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  • Atomic, Molecular and Optical Physics  (441)
  • Rat  (193)
  • 1990-1994  (634)
  • 1965-1969
  • 1992  (634)
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  • 1990-1994  (634)
  • 1965-1969
Year
  • 1
    ISSN: 1432-0738
    Keywords: Cadmium ; Rat ; Bone ; Long-term administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A decrease in mechanical strength of bones was observed both in young and old rats for long periods of administration of cadmium. Young (3-week-old) female rats were given 0 (control), 5 and 10 ppm cadmium in drinking water, respectively, for 20 weeks. Old (18-month old) female rats were given 0 (control) and 40 ppm cadmium in drinking water, respectively, for 7 months. The compression strengths of bones of young rats which were given 10 ppm cadmium, and those of old rats which were given 40 ppm cadmium, significantly decreased at the distal end portion of femur. Cadmium contents in bones in the 10 ppm and 40 ppm groups were about 110 and 210 ng/g dry weight, respectively. The present result confirmed that cadmium has a lesional effect on the mechanical strength of bone at the concentration of 100–200 ng/g in dry weight of bone, for both young and old rats.
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  • 2
    ISSN: 1432-0738
    Keywords: Ethoxyquin(6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) ; Nephrotoxicity ; Rat ; Proteinuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxicity of ethoxyquin (EQ) to rat kidney was examined in males which were either weanling or adult at the beginning of the experiment, and also in adult females. Female rats were much less susceptible to the toxic effects of EQ than males of the same age. In males damage to the cortex, mainly as an acceleration of the normal ageing process, was similar in both age groups, but rats exposed to EQ as weanlings also suffered from extensive papillary necrosis. Male rats were more prone than females to proteinuria, which was greatly exacerbated by EQ in both age groups. Thus there is very little evidence of nephrotoxicity in adult female rats on exposure to EQ at 0.5% in the diet for 26 weeks. In males, the initial age of the animal, as well as the length of treatment, influences the extent of damage.
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  • 3
    ISSN: 1432-0738
    Keywords: Aluminum ; Toxicokinetics ; Rat ; Parenterals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12000 μg Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12000 μg Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two-compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12000 μg/kg. At IV doses between 10 and 1000 μg/kg the terminal half-life of elimination from whole blood (t1/2β) increased from 29.9±7.8 to 209.3±32.6 min, and the total body clearance (CL) decreased from 2.45±0.64 to 0.28±0.03 ml min−1 kg−1. Following an IV bolus of 10 and 100 μg/kg the administered Al was recovered completely from urine (94.4%±9.9% and 98.5%±3.2%). Twenty-nine days after the IV dose of 1000 μg/kg daily renal excretion decreased to baseline values while only 55.1%±8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 μg/kg Al accumulated in liver (28.1±7.7 versus 1.7±0.5 μg/g of control rats) and spleen (72.5±21.1 versus 〈0.4 μg/g). After the single 1000 μg/kg IG dose no absorption of Al was detectable. The IG dose of 12000 μg/kg resulted in a maximum blood Al level of 47.9±12.4 μg/l after 50 min. The blood concentration time curve fitted a one-compartment open model with a half-life of absorption of 28.2±3.6 min and a t1/2β of 81.2±20.2 min. Cumulative renal Al excretion was 0.18%±0.10% of the dose and oral bioavailability was 0.02%. Seventeen days after the 12000 μg/kg IG dose the Al content in femur samples was increased (2.7±1.3 versus 0.6±0.4 μg/g). In no case was fecal elimination of incorporated Al observed.
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  • 4
    ISSN: 1432-0738
    Keywords: N-Nitrosamine ; Cytochrome P-450 ; Rat ; Phenobarbital ; β-Naphthoflavone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or β-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.
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  • 5
    ISSN: 1432-1106
    Keywords: Retina ; Ganglion cells ; Alpha cells ; Lucifer yellow ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The somato-dendritic morphologies of large ganglion cells were studied by intracellular injections of Lucifer yellow in perfusedin vitro preparations of the albino rat retina. The ganglion cells were prelabeled with retrogradely transported granular blue or labeled with acridine orange dropped into the perfusate ofin vitro preparations. After the dye injection, somato-dendritic morphologies were successfully studied for 210 cells, the majority of which had a large soma more than 20 µm in diameter and were identified as alpha cells. According to the level of dendritic extensions within the inner plexiform layer (IPL) these alpha cells were further classified into inner ramifying (inner) and outer ramifying (outer) cells. Both qualitative and quantitative observations led us to conclude the following:1) The outer cells have a spherical soma with relatively few primary dendrites, while inner cells have a large polygonal soma with more primary dendrites.2) The dendritic field of inner cells was always larger than that of outer cells at every retinal location. The dendritic field diameter tended to increase as a function of retinal eccentricity from the optic disk, the tendency being more clear among inner cells.3) The dendrites of outer cells branch more frequently in the proximal part of the dendritic field while those of inner cells branch more distally.4) Total dendritic length of outer cells increases linearly with eccentricity whereas that of the inner cells does not change much irrespective of retinal location.
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  • 6
    ISSN: 1432-1106
    Keywords: Corpus callosum ; Frontal agranular cortex ; GABA receptor ; NMDA receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A slice preparation of rat frontal agranular cortex preserving commissural inputs has been used for intracellular recording from layer V pyramidal cells, in order to characterize the synaptic potentials induced by stimulation of the corpus callosum and to reveal the subtypes of amino acid receptors involved. Stimulation of the corpus callosum induced EPSPs followed by early IPSPs with a peak latency of 30 ± 2 ms and late IPSPs with a peak latency of 185 ± 18 ms. Reversal potentials for early and late IPSPs were −75 ± 5 mV (early) and −96 ± 5 mV (late). Late IPSPs were more dependent on extracellular K+ concentration. The early IPSPs were blocked by GABAA antagonists, bicuculline and picrotoxin, whereas the late IPSPs were reduced by the GABAB antagonist, phaclofen. CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an antagonist of non-NMDA (N-methyl-D-aspartate) receptors, suppressed both EPSPs and late IPSPs at 5 µM. Early IPSPs remained at this concentration but were suppressed by 20 µM CNQX. In Mg2+-free solution, EPSPs were larger and more prolonged than in control solution. These enhanced EPSPs persisted after 5 to 20 µM CNQX, but were reduced in amplitude, and their onset was delayed by 3.6 ± 0.8 ms. The remaining EPSPs were suppressed by 50 µM APV (DL-2-amino-5-phosphono-valeric acid), an antagonist of NMDA receptors. In Mg2+-free solution containing 5 to 20 µM CNQX, the late IPSPs were not diminished. The remaining late IPSPs were suppressed by APV or by phaclofen. By contrast, the amplitude of early IPSPs was not affected by APV in Mg2+-free solution containing 5 µM CNQX. These results show that stimulation of the corpus callosum can induce GABAA and GABAB dependent IPSPs and NMDA and non-NMDA dependent excitation. It is suggested that these four types of amino acid-based transmission are conveyed by intracortical pathways with different characteristics.
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  • 7
    ISSN: 1432-1106
    Keywords: Cerebral ischemia ; Glutamate ; Heat shock protein ; Hippocampus ; Programmed cell death ; Rat ; Ubiquitin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutanously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.
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  • 8
    ISSN: 1432-1106
    Keywords: Genetically epilepsy-prone rat ; Blood-brain barrier ; Local cerebral glucose utilization ; Thyroid hormones ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The genetically epileptic-prone rat (GEPR) is a valuable model for the study of gene-linked abnormalities involved in epilepsy. In comparison with normal Sprague-Dawley controls, we found, in GEPRs, a marked depression in local cerebral glucose utilization, widespread throughout the brain. This depression was accompanied by a significant increase of blood-brain barrier permeability and a reduction in regional blood volume. Finally GEPRs showed lower plasma levels of total triiodothyronine than normal controls. One can speculate that alterations in cerebral metabolism and microvascular regulation and thyroid hormone imbalance may be gene-linked factors involved in seizure susceptibility.
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  • 9
    ISSN: 1432-1106
    Keywords: Endothelin ; Ischemia ; Striatum ; Microdialysis ; Cerebral blood flow ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study examines the possibility that lesions induced by intrastriatal injections of endothelin-1 (ET-1, 0.43 nmol/0.5 µl) are ischemic in nature due to a vasoconstriction of the cerebral microvessels. In time course and dose-response experiments with ET-1 and in comparisons with ET-3, the volume of the lesions has been determined based mainly on the disappearance of striatal nerve cells, using a computer assisted morphometrical analysis. The blood flow in the neostriatum close to the site of injection of ET-1 was determined acutely by Laser-Doppler flowmetry. The acute metabolic effects of ET-1 were also studied on striatal superfusate levels of lactate, pyruvate, dopamine and its metabolites DOPAC (3,4-dihydroxyphenylacetic acid) and homovanilic acid (HVA) using an instrastriatal microdialysis probe. Dose related striatal lesions were observed with ET-1 (0.043–0.43 nmol) with a peak lesion volume after 24–48 h and the possible existence of a penumbra area. ET-3 showed a reduced potency to produce striatal lesions compared to ET-1. The lesions induced by ET-1 were prevented by coinjection with dihydralazine, a vasodilator drug. Acutely ET-1 (0.43 nmol/0.5 µl) produced a prolonged reduction of the cerebral blood flow down to 40% of control values and temporary increases of striatal lactate and DA efflux, the latter change being very marked. Also a significant reduction of DOPAC and HVA was observed. These neurochemical changes were all prevented by treatment with dihydralazine. These results indicate that ET-1 injected in the neostriatum may produce lesions by causing local ischemia, related to its vasoconstrictor activity and possibly also to an activation of ET-1 receptors in the astroglial-endothelial complex. Based on the present results it seems possible that ET-1 may participate in the multifactorial pathogenesis of cerebral ischemia.
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  • 10
    ISSN: 1432-1106
    Keywords: Cerebellum ; Nucleus lateralis ; Rat ; Motor organization ; Microstimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The motor organization of the nucleus lateralis (NL) of the rat's cerebellum was investigated by observing the motor effects of electrical microstimulations of the NL. The movements evoked by the NL mainly concerned forelimb and head segments. Only in a few cases were movements of hindlimb segments evoked. Motor effects were obtained according to a precise topographical pattern. This pattern delimited functional zones, or representations, within the NL, each zone being specifically related to a particular segment of the body. A few body segments were activated from single zones only (single representation) whereas some other body segments could be activated from different zones of the NL. Among them, the axio-proximal body segments were activated in a similar way from all sites (multiple representation) whereas the distal body segments were differently activated from the various representation zones (specific representation). The multiple and specific representations were distributed between the 3 cytoarchitectonic subregions of the NL (NLm, DLH and slp) in such a way that the body segments were usually represented only once in each individual NL subregion. Each NL subregion included sets of representations concerning body segments characterized by a topographical continuity (e.g. the different segments of the forelimb in both DLH and slp). Thus, the individual NL subregions may bring into play coordinate plurisegmental muscular activities of the limbs and/or of the head. The NLm controls movements of all the segments of the head and those of axio-proximal segments of both limbs. The DLH particularly controls movements of the head, including both the proximal (neck) and the oral regions. To a lesser degree, DLH controls movements of the various segments of the forelimb, including synchronous flexion of all the digits. The slp is specifically involved in the control of motor activities of: i) the proximal segment of the head (rotation of the neck) as well as its distal segments (displacement of individual vibrissae, rotation of the ear pinna) and ii) the various segments of the forelimb including individual digits. Functionally, the proximal segments would be concerned in the spatial displacement of the limbs or of the head whereas the distal segments would be involved in the realization of precise and discrete movements related to specific functions of the distal segments concerned. The 3 subregions of the NL may be concerned in different motor functions. The results suggest the involvement of: i) the NLm in the postural adjustments of the body, or of part of it; ii) the DLH in motor behaviours which integrate the oral and the forelimb motor activities; iii) the slp in exploratory activities (by moving individual vibrissae, the ear pinna and individual digits) and/or in discrete manipulative activities.
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  • 11
    ISSN: 1432-1106
    Keywords: Visual part of nucleus reticularis thalami ; Unit activity ; Conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In urethane anesthetized rats neuronal responses of the visual part of nucleus reticularis thalami (vTR) to light were compared with those during pairing light as a conditioned stimulus (CS) with the electrical stimulation of the rat's tail (US). The intensity of the US was adjusted to the minimum required to evoke a slight freezing behavior in the awake rat. The firing rate of most vTR neurons decreased in the period between light and US application (P 〈 0.01). Significant response modulations to light were observed in 39% of the units, in most of them they persisted over an extinction period of 15 min. In addition, neurons which were predominantly inhibited by conditioning sometimes changed from regular spiking to a burst pattern. The results support the hypothesis that conditioning related facilitation of geniculate neurons observed in previous experiments can be explained at least partly by disinhibition of geniculate units from vTR.
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  • 12
    ISSN: 1432-1106
    Keywords: Miniature EPSP ; Spinal cord cultures ; Motoneuron ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Miniature excitatory postsynaptic potentials (mEPSPs) were recorded in motoneurons grown in organotypic cocultures of embryonic rat spinal cord, dorsal root ganglia and muscle in the presence of TTX. The motoneurons were electrically compact with a mean electrotonic length of 0.6. Spontaneous EPSPs were found in most of these motoneurons. With TTX the large EPSPs disappeared, whereas in more than half of the experiments mEPSPs persisted with a range in size of 1 to 4 mV (mean: 2.1 mV), probabely originating from the spontaneous release of single vesicles. The net inward charge transfer at the soma ranged from 0.12 to 0.34 pC. The mEPSPs were heterogeneous in size even within pools of potentials that were homogeneous in shape. They had similar shapes and amplitudes as the smallest spontaneous unitary EPSPs mediated by presynaptic impulses, suggesting that for the smallest afferents not more than one vesicle was released per afferent impulse. Both the miniature and the TTX-sensitive EPSPs were readily blocked by the glutamate antagonist DNQX.
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  • 13
    ISSN: 1432-1106
    Keywords: Fetal breathing ; Respiratory centers ; Development ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A fetal rat brain stem-spinal cord in vitro preparation (15–20 days) which retains for several hours respiratory-like discharges on cervical and cranial ventral roots has been developed for analysing fetal central respiratory activity. Two different patterns of easily distinguishable rhythmic activity were recorded. The first, of spinal origin, appeared every 2–10 min as long bursts of potentials (3–30 s) on cervical, but not hypoglossal, roots. The second pattern corresponded to brief bursts (1 s) of potentials occurring on both cervical and hypoglossal roots at a frequency ranging from 3–4 cycles min-1. The second type of activity was likely to be respiratory since it originated from the medulla, and behaved similarly to the respiratory activity recorded in vitro from newborn rats. The fetal respiratory-like activity was never observed at day 15, appeared at day 16 in 30% of the preparations with fluctuating frequency and amplitude bursts, and stabilised at day 20 where it was usually present and resembled newborn rat respiratory activity: its frequency was stable but was reduced by withdrawal of CO2 and pH stimuli and modulated by a pontine noradrenergic influence. This fetal preparation offers many advantages for studying the ontogeny of the central respiratory activity because of the background knowledge available on the adult and newborn rat respiratory centers and the possibility of performing electrophysiological, morphological and pharmacological fetal studies directly at the central level without any feedback from the periphery.
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  • 14
    ISSN: 1432-1106
    Keywords: Basic fibroblast growth factor ; Forebrain ischemia ; Astrocyte ; Immunoreactivity ; mRNA level ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the time course of basic fibroblast growth factor (bFGF) immunoreactivity and its mRNA level mainly in the hippocampus after transient forebrain ischemia using immunohistochemistry, enzyme immunoassay (EIA), Western blot analysis and in situ hybridization. Neuronal death in the hippocampal CA1 subfield was observed 72 h after 20 min of ischemia. The number of bFGF-immunoreactive(IR) cells increased 48 h–5 days after ischemia in all hippocampal regions. At 10 and 30 days, the bFGF-IR cells in the CA1 subfield had further increased in numbers and altered their morphology, enlarging and turning into typical reactive astrocytes with the advancing neuronal death in that area. In contrast, the number of bFGF-IR cells in other hippocampal regions had decreased 30 days after ischemia. The EIA study showed a drastic increase in bFGF levels in the hippocampus 48 h after ischemia (150% of that in normal rat) which was followed by further increases. In Western blot analysis, three immunoreactive bands whose molecular weights correspond to 18, 22 and 24 kDa were observed in normal rat and ischemia increased all their immunoreactivities. In the in situ hybridization study of the hippocampus, bFGF mRNA positive cells were observed in the CA1 subfield in which many bFGF-IR cells existed after ischemia. These data demonstrate that transient forebrain ischemia leads to an early and strong induction of bFGF synthesis in astrocytes, suggesting that the role of bFGF is related to the function of the reactive astrocytes which appear following brain injury.
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  • 15
    ISSN: 1432-1106
    Keywords: Homocysteic acid ; Cerebellum ; Taurine ; Glial cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An antiserum to homocysteic acid was raised in rabbits. Immunogens were prepared by coupling this amino acid to bovine serum albumin by means of glutaraldehyde and paraformaldehyde. When applied to semithin or ultrathin sections of rat cerebellum, the antiserum produced selective labelling of glial cells and processes, including the Bergmann fibers. No enrichment of immunoreactivity was detected in nerve terminals of the major excitatory fiber systems. The distribution of homocysteic acid-like immunoreactivity was very different from that of taurine (another sulphur-containing amino acid), as judged from consecutive semithin sections labelled with a postembedding immunoperoxidase procedure and from ultrathin sections labelled with a postembedding double immunogold procedure. Taurine-like immunoreactivity was concentrated in Purkinje cells and was low in glial elements. Our data suggest that the cerebellum contains a glial pool of homocysteic acid (and/or precursors that may undergo spontaneous oxidation to homocysteic acid) and that this amino acid is unlikely to act as a cerebellar transmitter.
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  • 16
    ISSN: 1432-1106
    Keywords: Direct Cortical Response ; Sensory Evoked ; Response ; Current Source Density ; Somatosensory Cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A current-flow and current-source-density analysis of the sensory evoked response (SER) and the direct cortical response (DCR) in the somatosensory cortex of rats was performed to determine the origin of these potentials. The SER was found to originate in layers II and III, as in cats, with a single excitatory neuronal circuit component. The DCR, on the other hand, has five components, three inhibitory and two excitatory. The activation and magnitude of these components vary with stimulus strength and frequency. During the second and fourth ms of the response, two inhibitory currents flow in layers V and VI; 2 ms later, excitatory current flows in layers II and III. This excitatory current appears to be the same one involved in the SER. Five ms later, the superficial excitatory current is replaced by an inhibitory one in the neighborhood of the DCR's negative peak. At strong stimulus strengths, this is followed by an excitatory current in layer V. The early inhibitory and excitatory components step up through layers upper-VI, V and III over time, implying that inhibition followed by excitation moves upward through cortex. The currents associated with the DCR in somatosensory cortex are compared with those for the DCR in motor and association cortex.
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  • 17
    ISSN: 1432-1106
    Keywords: Neural grafting ; Neural transplantation ; Parkinson's disease ; Cryopreservation ; Fetal mesencephalon ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we quantitatively assessed to what extent freeze-storage at liquid nitrogen temperature influences the survival and function of fetal mesencephalic grafts in the dopamine-depleted rat striatum. Ventral mesencephalic (VM) tissue was dissected from rat fetuses and stored overnight in a preservative medium at 4 °C (hibernation). It was grafted intrastriatally either as a fresh cell suspension or was frozen as tissue fragments or as a cell suspension after stepwise incubation in ascending concentrations of dimethyl-sulphoxide. Following a cryopreservation interval of 80 days in liquid nitrogen, the frozen samples were rapidly thawed, rinsed, and grafted. Cellular viabilities of graft cell suspensions, as assessed by ethidium bromide/acridine orange staining, were decreased from 90% in fresh tissue to 38-35% in frozen and thawed tissue. Amphetamine-induced turning behavior at 6 weeks post-grafting was significantly attenuated in hosts that had received fresh grafts or grafts that were frozen as tissue fragments. Tyrosine hydroxylase-(TH-) immunocytochemistry of recipient brains revealed significant decreases in TH-positive graft cell numbers in rats grafted with cryopreserved tissue (38–42% of fresh tissue). Moreover, the dye exclusion viability of thawed VM tissue was found to accurately predict the subsequent graft survival. There was no difference with respect to graft cell numbers between the two freezing methods employed, though block storage seems to be more simple from a practical point of view. The present study indicates that freezing in liquid nitrogen may be a feasible method for long-term storage of fetal neural tissue for grafting, although a marked decrease in graft survival and function of cryopreserved tissue must be taken into account.
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  • 18
    ISSN: 1432-1106
    Keywords: Colchicine ; Choline acetyltransferase ; Cholinergic degeneration ; Phosphoinositide hydrolysis ; Cytoskeletal proteins ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Colchicine, a microtubule disrupting toxin, was administered intracerebroventricularly to rats, followed by measurements of (i) the activity of choline acetyltransferase, a biochemical marker of cholinergic neurons, (ii) cytoskeletal protein concentrations, including tau, MAP-2, spectrin, and tubulin, and (iii) the activity of the second messenger-generating system, receptor-coupled phosphoinositide hydrolysis. One week after colchicine treatment there was a 60% decrease in choline acetyltransferase activity in the hippocampus, which was followed by a gradual increase to only a 29% deficit after 12 weeks. In the striatum and cerebral cortex, choline acetyltransferase activity was slightly reduced (by 13% and 19%, respectively) 1 week after colchicine treatment followed by increases to control values. The concentrations of tau and tubulin in the hippocampus were unaltered by colchicine treatment, and MAP-2 and spectrin were only slightly reduced 4 weeks after colchicine. Hippocampal phosphoinositide hydrolysis induced by norepinephrine was elevated approximately 28% 1 and 2 weeks after colchicine treatment and that induced by ibotenate was increased by 53% 2 weeks after colchicine. These results demonstrate that colchicine causes a severe depletion of choline acetyltransferase 1 week after administration. There was not a significant reduction of the concentration of any of the cytoskeletal proteins after 1 week, possibly due to the cell-selectivity of the toxic effect of colchicine, but there was a delayed, and temporary, decline of MAP-2 and spectrin concentrations. Associated with the decreased choline acetyltransferase activity after 1 week was an enhanced phosphoinositide hydrolysis in response to norepinephrine, and after 2 weeks there were enhanced responses to norepinephrine and to ibotenate. Thus, colchicine-induced toxicity results in neurotransmitter- and time-specific alterations in the activity of the phosphoinositide second messenger-generating system in the hippocampus.
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  • 19
    ISSN: 1432-1106
    Keywords: Movement ; Sequence ; Basal ganglia ; Frontal cortex ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats emit grooming actions in sequences that follow characteristic patterns of serial order. One of these patterns, a syntactic chain, has a particularly stereotyped order that recurs spontaneously during grooming thousands of times more often than could occur by chance. Previous studies have shown that performance of this sequence is impaired by excitotoxin lesions of the corpus striatum. In this study we examined whether the striatum is unique in its importance to this behavioral sequence or whether control of the sequence instead depends equally upon the cortex and cerebellum. In two experiments, a fine-grained behavioral analysis compared the effects of striatal ablation to the effects of motor cortex ablation, ablation of the entire neocortex, or ablation of the cerebellum. Cortical and cerebellar aspiration produced mere temporary deficits in grooming sequences, which appeared to reflect a general factor that was nonsequential in nature. Only striatal damage produced a permanent sequential deficit in the coordination of this syntactic grooming chain. We conclude that the striatum has a unique role in the control of behavioral serial order. This striatal role may be related to a number of sequential disorders observed in human diseases involving the striatum.
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  • 20
    ISSN: 1432-1106
    Keywords: Area postrema ; Lesion ; Supraoptic nucleus ; Oxytocin ; Osmotic stimulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed to examine whether or not the area postrema (AP) is involved in the osmotic control of neurohypophysial hormone release. In control rats and in rats bearing extensive lesions of AP, extracellular action potentials were recorded from neurosecretory cells in the supraoptic nucleus (SON) and firing rates determined before and after the intraperitoneal (i.p.) injection of 1.5 M-NaCl solution. Lesion of the AP significantly (p≦0.05, Mann-Whitney's U-test) lowered firing rate of putative vasopressin (phasic) cells but not that of oxytocin (non-phasic) cells. In lesioned animals, i.p. injection of hypertonic saline, however, caused similar changes in plasma osmotic pressure, plasma oxytocin concentration and mean firing rates of both putative oxytocin and vasopressin cells to those in control rats. The results suggest that the osmotic control of SON neurosecretory cell activity in the rat can take place in the absence of the AP.
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  • 21
    ISSN: 1432-1106
    Keywords: Cholinergic systems ; Acetylcholinesterase ; Choline acetyltransferase ; Superior colliculus ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the distribution of acetylcholinesterase activity and choline acetyltransferase immunoreactivity in the superior colliculus of the guinea pig and the albino rat, using enzyme histochemical and immunohistochemical methods. Choline acetyltransferase-like immunoreactivity was localized in the neuropil throughout the colliculi, but the density of the immunoreactive neuropil varied among layers as well as between species. In the intermediate collicular layers the pattern of choline acetyltransferase immunoreactivity was closely matched by the distribution of acetylcholinesterase activity in guinea pig and rat, confirming our previous findings in the cat. Furthermore, in the guinea pig, but not in the rat, choline acetyltransferase-like immunoreactivity was localized in a prominent population of perikarya of the superficial gray layer.
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  • 22
    ISSN: 1432-1106
    Keywords: Methylazoxymethanol acetate ; Microencephaly ; Choline acetyltransferase ; Substance P ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The habenulo-interpeduncular system of the rat constitutes an interesting model to address quantitatively problems related to synaptogenesis and to the interactions between neuronal populations after selective alteration of these elements during development. In the present study this has been achieved by experimentally reducing, through gestational treatment with methylazoxymethanol acetate (MAM), the population of cholinergic neurons of the medial habenula which projects to the interpeduncular nucleus. Immunohistochemical analysis gave evidence that the topographical localization of the cholinergic and the substance P-containing populations in the medial habenula was not altered by MAM treatment. Furthermore, the topographical distribution of cholinergic fibers and terminals in the interpeduncular nucleus, which reflects the habenulo-interpeduncular projection as well as cholinergic projections coming from different sources, was substantially preserved. The same was also true concerning the terminal distribution of substance P in the interpeduncular nucleus. Quantitative radioassays demonstrated a sizable decrease of overall ChAT activity in both the habenulae and the interpeduncular nucleus. By comparison of 1 month-old and 3 month-old animals it appeared that this effect was partially reversed with age in the interpeduncular nucleus.
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  • 23
    ISSN: 1432-1106
    Keywords: Synaptic-Plasticity ; Cerebellum ; Metabotropic-glutamate-receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using an in vitro slice preparation, we studied the effects, on parallel fiber (PF)-mediated EPSPs, of coactivation of metabotropic-glutamate receptors and of voltage-gated calcium (Ca) channels of Purkinje cells (PCs) by bath application of 50 μM trans-1-aminocyclopentyl-1,3-dicarboxylate (trans-ACPD) and by direct depolarization of the cells, respectively. These effects were compared with changes in synaptic efficacy obtained when α-amino-3hydroxy-5-methylisoxalone-4-propionate (AMPA) receptors of PCs were also activated through stimulation of PFs during the pairing protocol, as well as when similar experiments were performed without trans-ACPD in the bath. In a control medium, pairing for 1 min of PF-mediated EPSPs evoked at 1 Hz with Ca spikes evoked by steady depolarization of PCs (n = 13) led to LTD of synaptic transmission in 9 cases whereas for the others EPSPs were not affected. No LTD occurred in 9 out of 10 other cells tested when PF stimulation was omitted during the 1 min period of Ca spike firing of PCs. Bath application of 50 μM trans-ACPD, in conjunction with the same pairing protocol as before (n = 8), led to a significantly larger LTD of PF-mediated EPSPs after washing out of this drug. Moreover, a clearcut LTD of PF-mediated EPSPs was also observed in 5 of the 8 other cells, when PF stimulation was omitted during Ca spike firing in the presence of trans-ACPD. As trans-ACPD alone induced fully reversible depressions of EPSPs, coactivation of metabotropic-glutamate receptors and of voltage-gated Ca channels is therefore likely to be sufficient to induce LTD of PF-mediated EPSPs.
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  • 24
    ISSN: 1432-1106
    Keywords: Periaqueductal gray matter ; Defensive behavior ; Excitatory amino acids ; Freezing ; Hypertensive reaction ; Ultrasonic vocalization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a previous study we investigated the intraspecific defensive reactions evoked by excitation of neurons in the intermediate third of the midbrain periaqueductal gray matter (PAG) of the rat. Experiments revealed that activation of neurons in this region of the PAG mediated: (i) backward defensive behavior, characterized by upright postures and backward movements, and (ii) reactive immobility (“freezing”), in which the rat remained immobile, but reacted with backward defensive behavior to investigative, non-aggressive contact initiated by the partner. In the present study, we aimed to extend our understanding of PAG mediation of defensive behavior by observing: (i) in a non-aggressive social interaction test, the behavioral effects of microinjections of low doses of kainic acid (40 pmol in 200 nl) made in the caudal third of the PAG; and (ii) the behavioral and cardiovascular effects of microinjections of d, l-homocysteic acid (5–10 nmol in 50–100 nl) made in the PAG of the unanesthetized decerebrate rat. Kainic acid injections into the area lateral to the midbrain aqueduct in the caudal third of the PAG evoked: (i) forward avoidance behavior, characterized by forward locomotion and occasional hop/jumps; (ii) reactive immobility (“freezing”), in which the rat remained immobile, but reacted with forward avoidance behavior to investigative, non-aggressive contact initiated by the partner; and (iii) 22–28 kHz ultrasonic vocalizations. These injections also evoked a dramatic increase in defensive responsiveness to tactile stimuli on the half of the body contralateral, but not ipsilateral, to the site of injection. Electroencephalographic measurements indicated that none of these effects were secondary to seizure activity. In the decerebrate rat, d, l-homocysteic acid injections in the caudal third of the PAG evoked forward running movements along with increased blood pressure and heart rate, the strongest effects being evoked from the region lateral to the midbrain aqueduct. More rostrally, sites in the intermediate PAG evoked backward “defensive” movements, which were also associated with increased blood pressure and heart rate. These data, along with those from our previous study in the rat indicate that: (i) defensive reactions are integrated within a longitudinal neuronal column which spans the caudal two thirds of the lateral PAG; (ii) the lateral PAG “defensive behavior” column contains two distinct populations of neurons, one within the intermediate lateral PAG which integrates defensive behavior characterized by facing towards and backing away from a “threatening” stimulus, and a second in the caudal lateral PAG which integrates defensive behavior characterized by forward avoidance behavior; and (iii) neurons within the lateral PAG couple strong cardiovascular changes with each distinctive defensive behavior pattern. The emerging view from this and recent studies of this midbrain region in other species, suggests that similar rostrocaudal differences within a longitudinally oriented lateral PAG neuronal column represent a fundamental principle underlying the PAG organization of defensive behavior.
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  • 25
    ISSN: 1432-1106
    Keywords: Motoneuron ; Motor axon ; Nerve conduction ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Axon conduction distance, conduction velocity, and conduction time were measured for individual triceps surae motoneurons in Sprague-Dawley rats weighing 230–630 g (i.e., age range 6–16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r=0.95 and r=0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is probably due to a corresponding increase in axon diameter. It could contribute to maintenance of stable motor performance during rapid growth.
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  • 26
    ISSN: 1432-1106
    Keywords: Retina ; Transplant ; Parvalbumin ; Immunocytochemistry ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retinas from embryonic day 14 Sprague-Dawley rats were transplanted to the midbrain or cerebral cortex of newborn (P0) rats of which the right eye was enucleated at the time of transplantation. Parvalbumin immunoreactive (PV-I) neurons were studied in the developing retinal transplants, and in the remaining retina of the host, as well as in normal retinas. PV-I neurons were identifiable in retinas of normal and host rats from postnatal day 5 (P5) onward, with the PV-I somata primarily in the inner half of the inner nuclear layer and in the ganglion cell layer. An adult-like distribution of PV-I neurons was attained at P35, as judged by cell packing density, intensity of immunostaining, laminar distribution and soma size of subpopulations of PV-I cells. A similar time course of development and distribution of PV-I somata was observed in the retinal transplants, except for some minor differences such as a slight delay in PV-I cells achieving their final distribution. These findings provide evidence that PV-I neurons can survive, differentiate and mature according to pre-determined programmes intrinsic to the retinal tissue following transplantation to a new and foreign environment.
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  • 27
    ISSN: 1432-1106
    Keywords: Dopamine-rich transplants ; Fos protein ; Nigrostriatal system ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present experiment was to characterize the effect of intrastriatal grafts of embryonic dopaminergic neurones on the expression of Fos protein in the striatum when challenged with amphetamine. Unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were made in adult rats and grafting was performed 3 weeks later. The numbers of Fos-positive nuclei in the ipsi- and contralateral striata were counted on coronal sections following immunohistochemical staining 5 months after grafting. Administration of d-amphetamine induced an increase in the density of Fospositive nuclei in the intact striatum. This stimulatory effect of amphetamine on c-fos expression was blocked by 6-hydroxydopamine hydrobromide lesions and was restored in the striata bearing transplants. However, an overshoot was observed as the density of Fos-positive cells within the grafted striatum was larger than that observed within the intact striatum. This hyperexpression of Fos-positive nuclei was correlated with the exaggerated compensation of amphetamine-induced rotation in the same animals.
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  • 28
    ISSN: 1432-1106
    Keywords: Vibrissae ; Somatosensory system ; Cortical columns ; Receptive field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A “barrel” is an interconnected network of layer IV neurons that is an important component of a functional cortical column in the whisker area of the rodent primary somatosensory cortex. The present study was undertaken in order to resolve apparently conflicting findings from single-unit studies of barrel neurons conducted in rats maintained under different anesthetic conditions. Multiunit responses to controlled deflections of mystacial vibrissae were recorded from the whisker/ barrel cortex of awake, undrugged rats, and responses at the same recording site were reexamined after the animal was anesthetized with urethane. In contrast to the awake condition, stimulus-evoked responses under urethane were characterized by a large late component. Such effects were more pronounced for deflections of noncolumnar or “adjacent” whiskers than for the the columnar whisker. Latencies to peak responses were virtually identical for the columnar whisker in awake and urethane states (11.9 vs 11.8 ms) but were considerably longer for adjacent whisker deflections in urethane-anesthetized animals (15.5 vs 29.0 ms). The magnitudes of adjacent whisker responses, relative to the response evoked by the columnar whisker, varied with the laminar location of the recording site in awake but not in urethane-anesthetized animals; in awake rats, receptive fields were clearly smallest in the layer IV barrels. Results in the awake condition confirm those of previous studies conducted in unanesthetized or lightly sedated animals, and data obtained with urethane are comparable to others' results in urethane-anesthetized rats. The former have important implications for how barrel cortex processes information in behaving animals.
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  • 29
    ISSN: 1432-1106
    Keywords: Transplantation ; Developmental neurobiology ; Retrograde labelling ; Immunocytochemistry ; Acetylcholinesterase histochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Embryonic spinal cord grafts from 12-day-old rat embryos were placed into the lumbar spinal cord of adult rats depleted of sciatic motoneurones by a neonatal nerve injury. A soleus muscle was removed from the leg and implanted paravertebrally, the proximal end of its nerve connected to the graft site. Fluorescent retrograde tracers injected into the soleus implant, 37–64 days postoperatively, labelled neurones that had grown axons to the muscle. Approximately one-fifth of retrogradely labelled neurones were within the graft; however, the majority were found within the host spinal cord close to the graft. These included large neurones within the motoneurone-depleted dorsolateral ventral horn. In control experiments a muscle and nerve were implanted but no embryonic tissue grafted. Significantly fewer neurones were labelled. In some animals, one tracer was injected into the soleus muscle whilst another was applied to the cut sciatic nerve ipsilateral to the graft site. No neurones were found to project axons to both targets. In animals that received grafts prelabelled with bromodeoxyuridine (BrDU) some neurones were found to be both BrDU positive and retrogradely labelled from the soleus implant. These were most frequently within the motoneuronedepleted ventral horn ipsilateral to the graft. Thus, grafted neurones may migrate to an appropriate location within the host neuropil. Acetylcholinesterase (AChE) histochemistry showed the graft site contained immature but AChE-positive neurones. Some regions of host ventral horn contained unusually few AChE-positive nerve fibres and occasional large AChE-positive neurones, some of which were also retrogradely labelled from the implanted muscle. Studies of implanted soleus 21–90 days after transplantation showed that muscle fibres, after initial degeneration, regenerated displaying differing phenotypes, presumably under the influence of new motor innervation.
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  • 30
    ISSN: 1432-1106
    Keywords: GAP-43 ; In situ hybridization ; Spinal cord ; Axotomy ; Rat ; Cat ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexed's lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord. The upregulation of GAP-43 mRNA found in contralateral, presumably uninjured motoneurons after peripheral nerve transection, as well as in dorsal horn neurons after a dorsal root transection, indicates that GAP-43 levels are altered not only as a direct consequence of a lesion, but also after changes in the synaptic input to the neurons.
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  • 31
    ISSN: 1432-1106
    Keywords: Subparafascicular nucleus ; Inferior colliculus ; Superior olivary complex ; Cochlear nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the course of our study on the neuronal connections of the subparafascicular nucleus (SPF) in the rat, descending projections from the SPF to the lower brain stem were examined by using the anterograde tracer PHA-L (Phaseolus vulgaris leukoagglutinin) and retrograde tracer WGA-HRP (horseradish peroxidase conjugated to wheat germ agglutinin). When PHA-L was injected into the magnocellular and/or parvicellular division of the SPF (SPFm and/or SPFp), presumed terminal labeling was seen, bilaterally with an ipsilateral dominance, in the mesencephalic and pontine central gray matter, peripheral shell regions of the inferior colliculus, cuneiform nucleus, and superior olivary complex (mainly in the superior paraolivary nucleus, and additionally in the nuclei of the trapezoid body). A few labeled axon terminals were also seen in the cochlear nuclei bilaterally with a contralateral dominance. In the second set of experiments, WGA-HRP was injected into the inferior colliculus, superior olivary complex, or cochlear nuclei. When WGA-HRP was injected into the peripheral shell regions of the inferior colliculus or the superior olivary complex, many labeled neuronal cell bodies were seen in the SPFm bilaterally with an ipsilateral dominance, and a moderate number of labeled neuronal cell bodies were observed in the SPFp (lateral SPF) bilaterally with an ipsilateral dominance. When WGA-HRP was injected into the cochlear nuclei, a moderate number of labeled neuronal cell bodies were observed in the SPFm and SPFp bilaterally with a contralateral dominance. The results indicate that the SPFm and SPFp (lateral SPF) of the rat send a considerable number of projection fibers to the lower brain stem. The target regions of these projection fibers include the auditory relay nuclei, such as the inferior colliculus, superior olivary complex, and cochlear nuclei.
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  • 32
    ISSN: 1432-1106
    Keywords: Medial vestibular nuclei ; Potentiation ; Depression ; AP5 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of high frequency stimulation (HFS) of the primary vestibular afferents on field potentials recorded in the ipsilateral Medial Vestibular Nuclei (MVN) was studied. Our results show that potentiation and depression can be induced in different portions of MVN, which are distinguishable by their anatomical organization. HFS induces potentiation of the monosynaptic component in the ventral portion of the MVN, whereas it provokes depression of the polysynaptic component in the dorsal portion of the same nucleus. The induction of both potentiation and depression was blocked under AP5 perfusion, thus demonstrating that NMDA receptor activation mediates both phenomena. Furthermore, the finding that the field potentials were not modified during perfusion with DL-AP5, as previously reported, supports the hypothesis that NMDA receptors are not involved in the normal synaptic transmission from the primary vestibular afferent fibres, but are only activated following hyperstimulation of this afferent system. Our results suggest that the mechanisms of long term modification of synaptic efficacy observed in MVN may underlie the plasticity phenomena occurring in vestibular nuclei.
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  • 33
    ISSN: 1432-1106
    Keywords: Opioid peptides ; Neurohypophysis ; Nerve endings ; Vasopressin ; Oxytocin ; Calcium ; Release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat neural lobes and isolated nerve terminals from the neurohypophysis were stimulated in the presence of different opioid agonists and antagonists. The secretion of arginine vasopressin and oxytocin and rise in cytoplasmic calcium induced by depolarization were analyzed by radioimmunoassay and the fluorescent probe fura-2, respectively. The kappa-agonists dynorphin A1 -13 and dynorphin A1 -8 did not affect electrically evoked release of vasopressin, although oxytocin release was slightly reduced. U-50 488, a relatively specific kappa-receptor agonist, had no effect on the amount of vasopressin or oxytocin secreted, although it significantly reduced K+-evoked changes in [Ca2+]i in isolated nerve endings. Two kappa-receptor antagonists, MR 2266 and diprenorphin, alone had no effect on vasopressin and oxytocin secretion from isolated nerve endings depolarized with potassium. Opioid agonists less selective for the kappa receptors, etorphin and ethylketocyclazocin, were found to inhibit the release of both vasopressin and oxytocin significantly. Naloxone, a nonselective opiate receptor antagonist, alone had no effect on vasopressin release but potentiated the electrically evoked release of oxytocin. Naloxone also could overcome the inhibitory effect of etorphin on oxytocin and vasopressin release observed after electrical stimulation of the neural lobe. A number of inconsistencies therefore exist between the effects of opioid agonists and antagonists on neuropeptide release and on the evoked changes in [Ca2+]i. In view of these inconsistencies and the high concentrations of opioid agonists and antagonists necessary to modify release, we conclude that it is doubtful that opioid molecules have a physiological role in controlling neurohypophysial secretion.
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  • 34
    ISSN: 1432-1106
    Keywords: Brain ischemia ; Idazoxan ; Metabolism ; Noradrenaline ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The brain noradrenaline (NA) system is known to modulate ischemic neuronal damage, and the turnover of NA has been suggested to increase in the early recovery period following cerebral ischemia. Using HPLC and gas chromatography-mass spectrometry we analyzed the tissue levels of NA and its metabolites, 3,4-dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in rat brain cortex after 10 min of forebrain ischemia followed by 1 h of recirculation. The effect of idazoxan, given in cerebro-pbrotective doses, as a bolus of 0.1 mg·kg-1 immediately after ischemia followed by 10 μg·kg-1·min-1 for 1 h, was also investigated. Ischemia decreased basal NA cortical levels from 384 ng/g tissue in control animals to 214 ng/g, while DHPG increased from 74 to 103 ng/g (+39%) and MHPG from 82 to 154 ng/g (+88%). Conjugated but not free DHPG increased, while both free and conjugated MHPG increased equally. The findings indicate an enhanced postischemic NA turnover with a major proportion of uptake and metabolism occurring extraneuronally, possibly secondary to a saturation of neuronal NA uptake in the postischemic phase. Idazoxan further increased NA turnover, as evidenced by higher postischemic levels of free MHPG and a higher MHPG/NA ratio. A correlation may exist between the protective action of idazoxan and its effect on NA turnover.
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  • 35
    ISSN: 1432-1106
    Keywords: Mesencephalic trigeminal neurons ; Peripheral nerve transection ; Cell loss ; Transganglionic degeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of peripheral nerve transection on mesencephalic trigeminal (MeV) neurons have been studied qualitatively and quantitatively in the rat. In the qualitative part of the study the brain stem was studied in Fink-Heimer stained sections 3–30 days after a masseteric nerve transection. Degeneration argyrophilia was observed both in the MeV tract and in the supratrigeminal and trigeminal motor nuclei, as well as in the lateral part of the brain stem reticular formation. The first signs of transganglionic degeneration (TGD) were seen 7 days postoperatively, and the amount of degeneration increased considerably with longer survival times. A quantitative analysis of the MeV nucleus was made 60 days after transection of the left masseteric nerve. This analysis showed a 10.5–22.7% reduction of cells on the side that had undergone masseteric nerve transection. The mean difference (left vs right side) was -2.4% in animals that had not been operated on. These findings show that mesencephalic trigeminal neurons with proprioceptive functions are very sensitive to peripheral nerve injury with a substantial cell loss and TGD as the result.
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  • 36
    ISSN: 1432-1106
    Keywords: Supraoptic nucleus ; Dynorphin ; Opioids ; Neurohypophysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Studies performed in conscious female rats confirmed that iv injection of cholecystokinin octapeptide (CCK; 20µ/kg) increased the circulating concentration of oxytocin but not that of vasopressin, and confirmed that the stimulation of oxytocin release was markedly facilitated after iv administration of naloxone (1mg/kg), indicating attenuation of oxytocin release by endogenous opioids. To investigate the site of action of the endogenous opioids, the electrical activity of putative oxytocin neurones in the supraoptic nucleus was recorded in urethaneanaesthetised female rats. Oxytocin neurones responded to CCK injection with an increase in firing rate lasting 5–15 min, but this response was not facilitated by prior injection of naloxone. The results suggest that the opioid influence upon CCK-induced oxytocin release operates at the level of the neurosecretory terminals in the neurohypophysis rather than centrally. Since CCK does not elevate vasopressin release, it appears unlikely that dynorphin, the opioid peptide co-existing with vasopressin, is responsible in these circumstances for the cross-inhibition of oxytocin release. It is suggested that products of proenkephalin A, the met-enkephalin precursor present in the supraoptic nucleus and in the neurohypophysis itself, may be active in the regulation of oxytocin release.
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  • 37
    ISSN: 1432-1106
    Keywords: Neuronal subsets ; Pericellular antigen ; Monoclonal antibody ; Cat ; 301 ; VC1.1 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We reported earlier that monoclonal antibodies (MAbs) 473 and 376 gave perineuronal staining of different subsets of central neurons, and that both immunoreactivities were labile to treatment with chondroitinase ABC. On the other hand, MAb 1B5, the immunoreactivity to which is uncovered by chondroitinase ABC, stained a neuronal subset that included neurons positive to MAbs 473 and 376 (Fujita et al. 1989). We now report a new antibody, MAb 374, that stained perimeter of neurons of a subset different from those stained by MAbs 473, 376 and 1B5. In the rat central nervous system MAb 374-positive cells were found in the neocortex, thalamic reticular nucleus, hippocampus, cerebellar cortex and nuclei, and in the brain stem. MAb 374-immunoreactive neuropil was found in the medial habenular, arcuate, dorsal endopiriform nuclei, and the two plexiform layers of the retina. The immunoreactivity was not affected by treatment with chondroitinase ABC. Immunoblot experiments using a rat brain homogenate revealed a specific band at a position corresponding to a molecular weight of 600 kD.
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  • 38
    ISSN: 1432-1106
    Keywords: Ischemia ; Brain damage ; Substantia nigra pars reticulata ; Excitatory amino acids ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Preischemic hyperglicemia worsens brain damage after ischemia, and characteristically leads to post-ischemic seizures and a pan-necrotic lesion in substantia nigra pars reticulata (SNPR). The excitatory input to SNPR could contribute to the damage observed. By performing a unilateral frontal cortex lesion 6–19 days prior to the ischemia, we wanted to explore whether a decrease in excitatory input to the ipsilateral SNPR ameliorate the seizures or alter the light microscopical damage in SNPR. Our results demonstrate that unilateral frontal cortex lesion did not alter the development of fatal post-ischemic seizures after 10 min of ischemia in hyperglycemic subjects. Thus, 7/8 animals developed seizures and died within 20 h of recovery. This study also failed to show any difference between the left and right side in post-ischemic SNPR damage after 15 h of recovery in animals with preischemic unilateral frontal cortex lesion. Furthermore, no side difference was observed in any other brain region evaluated. The results thus suggest that the pan-necrotic lesion in SNPR after hyperglicemic ischemia is not caused by excessive excitatory input from frontal cortex. A decrease in the GABA-ergic inhibitory input from caudoputamen to SNPR may be a more important mechanism for the ensuing excitotoxic post-ischemic SNPR damage, and for seizure development.
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  • 39
    ISSN: 1432-1106
    Keywords: 6-OHDA lesion ; Foetal ventral mesencephalic graft ; L-DOPA and carbidopa ; Parkinson's disease ; Circling behaviour ; Neural grafting ; Gliosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats with a unilateral 6-OHDA lesion of the nigrostriatal pathway, foetal ventral mesencephalic grafts implanted into the 6-OHDA-lesioned striatum produced a reduction in apomorphine-induced contralateral rotation, and complete abolition of (+)-amphetamine-induced ipsilateral rotation. The graft-induced reduction of apomorphine and (+)-amphetamine-induced rotation was not affected by chronic 27 week administration of L-DOPA and carbidopa to rats receiving foetal grafts. TH-immunohistochemistry revealed 〉96% loss of dopamine cells in the substantia nigra ipsilateral to the 6-OHDA lesion in all animals, but cell loss in the ipsilateral ventral tegmental area was more variable (21–46% of the intact side). TH-positive cells in the intact substantia nigra and ventral tegmental area were not affected by chronic treatment with L-DOPA and carbidopa. In the lesioned striatum of rats receiving sham grafts, no TH-positive cells or fibres were seen. In the 6-OHDA-lesioned striatum of animals receiving foetal grafts, many TH-positive cells were seen in the grafts and chronic treatment with L-DOPA and carbidopa did not reduce cell survival. GFA-P immunohistochemistry revealed that a unilateral 6-OHDA lesion followed by a sham graft was not associated with a reactive gliosis reaction in the striatum at the time of study (38 weeks after lesion surgery and 30 weeks after sham-graft), and treatment of such rats with L-DOPA and carbidopa was also without effect on glia. In contrast there was a marked gliosis in the striatum surrounding foetal grafts which was unaffected by chronic treatment with L-DOPA and carbidopa. The grafts themselves were surrounded by a rim of glial cells, and the glial density within the grafts was higher in animals receiving chronic L-DOPA and carbidopa treatment. However, there was no obvious relationship between the number of TH-positive cells within the grafts, or graft volume, and glial cell density within the grafts. These results suggest that long-term treatment with L-DOPA and carbidopa does not impair either the behavioural recovery produced by foetal ventral mesencephalic grafts in rats or the long-term survival of grafts as revealed by TH-immunohistochemistry. The presence of a foetal graft is associated with a reactive gliosis in the implanted striatum, which was not altered by long-term treatment with L-DOPA and carbidopa. However such treatment did result in an increase in glial density within the grafts themselves.
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  • 40
    ISSN: 1432-1106
    Keywords: Subparafascicular area ; Amygdala ; Striatum ; Fluorescent tracer ; Tyrosine hydroxylase immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dopaminergic nature of the pathway from the subparafascicular thalamic nucleus and its adjacent region to the amygdala was reexamined by means of retrograde fluorescent tracers coupled with tyrosine hydroxylase (TH) immunofluorescence. After injecting a small amount of tracer into the amygdala, retrogradely labeled cells were found in the subparafascicular thalamic nucleus and its adjacent periventricular region. TH immunofluorescence showed that these labeled cells completely lacked TH immunoreactivity. Similar results were obtained when a larger amount of tracer was applied to the amygdala. The present study, in contrast to the previous report describing the dopaminergic innervation of the amygdala by the cells in and around the subparafascicular area (A11 catecholamine cell group), indicates that the A11 cell group does not contribute to a dopaminergic input to the amygdala.
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  • 41
    ISSN: 1432-1106
    Keywords: Glutamate ; Hippocampal pyramidal cells ; Action potentials ; Prepotentials ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) The responses of CA1 pyramidal cells to short glutamate pulses (10–50 ms) delivered at sensitive spots in the apical dendrites have been analysed by intracellular recording. (2) The glutamate pulses elicited stable depolarizing responses in a dose- and frequencydependent manner. (3) When a single action potential with a firing probability around 0.5 was elicited, a subtraction procedure showed that a slow depolarizing ramp preceded each spike. We call this ramp the glutamate-induced prepotential (GluPP). (4) In contrast to the upward convex subthreshold depolarization the GluPP was upward concave. (5) The GluPP amplitude and time course increased with depolarization of the membrane, a phenomenon which appears to be connected to the elevation of action potential threshold. (6) The GluPP was regenerative since once started, it ended in an action potential. (7) A specific N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonovaleric acid (50 μM) reduced the glutamateinduced depolarization, but did not affect the form or amplitude of GluPP, once the latter was induced. (8) It is concluded that short glutamate pulses elicited action potentials through a prepotential mechanism, similar to the slow prepotentials induced by long depolarizing current pulses across the soma membrane. (9) A possible physiological role for the GluPP is discussed.
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  • 42
    ISSN: 1432-1106
    Keywords: Cervical ; Cuneate ; Trigeminal ; Primary afferents ; Somatosensory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed on rats to determine the location of thalamic projecting neurones in the medulla which receive direct contacts from neck primary afferents. The medullary terminations of primary afferents from the cervical region were identified by silver staining their degenerating terminals, diffusely filling their axons with horseradish peroxidase (HRP), or reacting for transganglionically transported HRP applied to muscle or cutaneous nerves. Neurones projecting to the ventrobasal thalamus were identified in the same experimental animals by using retrograde transport of HRP or Fluoro-Gold. En passant swellings or terminals of neck primary afferents were found in the vicinity of neurones projecting to the thalamus in the dorsolateral part of the rostral cuneate nucleus, the ventral aspect of the external cuneate nucleus, and the border zone between the two. Terminals of neck afferents and retrogradely labelled cells also coincided in nucleus x. Putative synaptic contacts were found in the region between the dorsolateral part of the rostral cuneate nucleus and ventromedial external cuneate nucleus. Cutaneous afferents from the neck were associated with thalamic projecting cells located along the dorsolateral border of the rostral cuneate nucleus, and afferents from neck muscles were associated with thalamic projecting cells in the caudal third of the external cuneate nucleus and in nucleus x.
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  • 43
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Intralaminar thalamus ; Tectal stimulation ; Somatosensory responses ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intralaminar thalamus of anesthetized rats was explored for neurons activated by stimulation of the superior colliculus and responsive to sensory inputs. Neurons activated by stimulation of the intermediate and deep collicular layers were distributed throughout the intralaminar thalamus. Approximately one half of them responded to tectal as well as sensory inputs. The majority were nociceptive or had a more complex response pattern including responses to auditory stimulation. A smaller population of low threshold units had contralateral orofacial receptive fields and responded to light taps; these units were preferentially localized anteriorly in the central lateral and paracentral nuclei. Neurons responsive to tectal and sensory stimulation were randomly intermingled with other neurons which had no detectable sensory input. The results indicate that ascending projection neurons of the intermediate and deep layers of the superior colliculus provide an input to functionally diverse subpopulations of intralaminar thalamic neurons. In view of its projections to motor cortex and basal ganglia, the intralaminar thalamus appears directly implicated in basal ganglia and superior colliculus related mechanisms of attention, arousal and postural orienting.
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  • 44
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Globus pallidus ; Neostriatum ; Movement Neuronal activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single-unit extracellular neuronal recordings were obtained from the globus pallidus (GP) and the neostriatum (NS) of rats while they performed a learned head movement in response to an auditory cue. In both GP and NS, units that altered their discharge rate in association with head movements and with the cues that triggered these head movements were prevalent. Frequently, the responses were directionally-specific (i.e., the magnitude or direction of change in firing rate of these neurons was substantially different for trials in which head movements were made to the left vs. the right). For some units, firing rates were altered only in response to the movement cue or only in association with head movements. However, the majority of neurons exhibited responses with both cue-related and movement-related components. Neuronal responses to the auditory cue usually were context-dependent, in that they did not occur if the same stimulus was presented when the animal was not performing the task. At least a small proportion of GP and NS neurons also appeared to exhibit context-dependent movement-related activity, in that responses occasionally were observed that were associated either with sensory-triggered head movements or with spontaneous head movements, but not with both. These data are consistent with previous suggestions that the activity of basal ganglia neurons during movement performance is highly dependent on the conditions associated with movement initiation. The data also indicate that the response characteristics of both GP and NS neurons in the rat are generally similar to those that have been described for basal ganglia neurons in primates and cats during sensory triggered movement tasks. However, the proportion of task-related neurons that exhibited responses with both movement-related and cue-related components was greater than has generally been reported in studies of cats and primates, suggesting that neurons with these response properties may be more predominant in the rat basal ganglia.
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  • 45
    ISSN: 1432-1106
    Keywords: Tectogeniculate projections ; SP ; VIP ; CCK ; WGA-HRP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Substance P (SP)-, vasoactive intestinal polypeptide (VIP)-, and cholecystokinin (CCK)-like immunoreactive (LI) neurons were found in the superior colliculus (SC) of the rat, and examined to ascertain whether they sent projection fibers to the dorsal lateral geniculate nucleus (LGNd). Immunocytochemical staining with antisera against SP, VIP, and CCK showed that many immunoreactive neuronal cell bodies were located in the superficial layers of the SC, especially in the stratum griseum superficiale. The pattern of distribution of these immunoreactive neuronal cell bodies in the SC was similar to that of neuronal cell bodies which were retrogradely labeled with WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) injected ipsilaterally into the LGNd. On the other hand, SP-, VIP- and CCK-LI axons were seen most densely in the lateral part of the LGNd, especially in the small-celled LGNd zone adjacent to the optic tract, where anterograde labeling was also observed after injection of WGA-HRP ipsilaterally into the superficial layers of the SC. When a lesion was produced by kainic acid injection into the superficial layers of the SC, axons showing SP-, VIP-, or CCK-LI in the LGNd ipsilateral to the lesion were markedly depleted. The results indicate that SC-LGNd projection neurons contain SP, VIP, and/or CCK in the rat.
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  • 46
    ISSN: 1432-1106
    Keywords: Vision ; Excitatory amino acids ; Thalamocortical connections ; Intrinsic connections ; Visual cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To examine the organization of axon collaterals of neurons that selectively take up and transport excitatory amino acids, we have used retrograde tracing with D-[3H]Aspartate after injections into different layers of rat primary visual cortex. The results show cells in the lateral geniculate nucleus retrogradely labeled from the cortex. Additional topographically precise input to the thalamic recipient layer 4 originates from neurons in the visual cortex lying in layers 2/3, 5 and 6. These inputs are reciprocated by point-to-point projections from layer 4. Layer 2/3 cells project to layers 5 and 6 in columnar fashion. Putative excitatory input to layer 2/3 originates from a vertical column of cells in layer 5 and the middle of layer 6. In addition layer 2/3 receives input via horizontal collaterals of topographically distant upper layer neurons, from more widespread projections in lower layer 6, and from very widespread projections of cells at the layer 5/6 border. Cells in the depth of layer 5 also distribute collaterals within layers 5 and 6. Our findings provide anatomical evidence that the geniculo-cortical pathway in the mammalian visual system may use excitatory amino acid transmitters. In addition, the results support the notion that most long range connections that link distant points of the topographic map are excitatory.
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  • 47
    ISSN: 1432-1106
    Keywords: GABA ; Iontophoresis ; Somatotopy ; SR95531 ; Ventrobasal thalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventropos-teromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependant on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the widespread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deaf-ferentation pain is discussed.
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  • 48
    ISSN: 1432-1106
    Keywords: Defence response ; Ventrolateral periaqueductal grey matter ; Rostral ventrolateral medulla ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal periaqueductal grey matter (PAG) evoked a presser response with tachycardia, vasodilatation in the hindlimb and hyperpnoea: a pattern of response known as the defence reaction. Microinjection of the synaptic excitant, D,L-homocysteic acid (DLH), but not saline, into the ventrolateral PAG at the level of the decussation of the superior cerebellar peduncle (approximately 7.3–8.3 mm caudal to bregma) produced a reduction in the size of the cardiovascular components of the defence reaction evoked by electrical stimulation in the dorsal PAG. Injections of DLH made outside this region had no effect on the defence response. Injection of DLH into the “defence inhibition area” had no effect on the presser response evoked distally in the efferent pathway for the defence reaction, by electrical stimulation in the rostral ventrolateral medulla (RVLM). Activation of neurones in a restricted portion of the caudal ventrolateral PAG appears to modulate activity in the descending pathway for the defence response evoked from the dorsal PAG. It is argued that the inhibitory interaction probably occurs at the level of synapses in the RVLM.
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  • 49
    ISSN: 1432-1106
    Keywords: Noradrenergic hyperactivity ; NE ; ACh ; Fornix section ; DSP4 ; Spatial memory ; Alzheimer's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats with unilateral or bilateral partial section of the fornix were impaired on an eight arm radial maze task. Neurochemical analysis of hippocampal tissue four weeks after the lesions revealed a 50% reduction of choline acetyltransferase (ChAT) activity. The cholinergic marker was correlated negatively with the number of errors in the maze; the lower the ChAT activity, the higher the error score. The fornix lesion also induced a 50% reduction in norepinephrine (NE), but no change in the noradrenergic metabolite methylhydroxyphenylglycol (MHPG), suggesting a net increase in turnover of NE in these animals. Additional lesion of the noradrenergic system with the neurotoxin DSP4 reduced both MHPG and NE levels by more than 90%, compared to nonlesioned controls, and reversed the behavioral deficit. This treatment had no further effect on cholinergic markers. There was a significant negative correlation between ChAT activity and the index of NE turnover, suggesting that hyperactivity in the noradrenergic system after fornix section inhibits the spared cholinergic function and thus exacerbates the cognitive deficit. The pattern of neurochemical results bear a striking resemblance to those seen in some Alzheimer's patients and suggest that an equilibrium among neurotransmitters is important to cognitive function.
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  • 50
    ISSN: 1432-1106
    Keywords: X-ray irradiation ; GABA ; Catecholamine ; Calcium binding proteins ; Olfactory bulb ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects on olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) – 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) – 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) – 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70–80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) – 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) – 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.
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  • 51
    ISSN: 1432-1106
    Keywords: Spike train ; Pattern recognition ; Hippocampal neurons ; Spontaneous activity ; Cell culture ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spontaneous activity and rhythmical oscillations are common features of large neuronal networks in mammals. Detection of repetitive spike patterns or pacemaker activity during electrophysiological recording of spontaneous action potentials from single neurons can be difficult if a “noisy” background is present. This paper describes an improved method for an online spike train analysis based on joint interval histograms (JIH, Rodiek et al. 1962). By means of higher ordered JIH the discrimination of spike patterns with repetitive bursting activity or oscillations is possible even when randomly distributed action potentials appear. Examples of simulated spike trains and those recorded from cultured hippocampal neurons are presented.
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  • 52
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 90 (1992), S. 147-152 
    ISSN: 1432-1106
    Keywords: Periaqueductal grey matter ; Rostral ventrolateral medulla ; Cardiovascular control ; Medullo-spinal neurones ; Defence reaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A study has been carried out to investigate the influence of the periaqueductal grey matter (PAG) on spinally-projecting neurones in the rostral ventrolateral medulla (RVLM) in rats anaesthetised with urethane. Microinjection of D,L-homocysteic acid was used to selectively activate nerve cell bodies in the PAG. Stimulation throughout the rostral half of the PAG and in the caudal PAG on a level with and dorsolateral to the level of the aqueduct evoked excitatory responses in 21 medullospinal cells in the RVLM. The neuronal excitation was associated with a rise in blood pressure. In contrast, stimulation within a restricted area of the ventrolateral PAG at the level of the dorsal raphe nucleus inhibited 10 medullo-spinal neurones in the RVLM, and produced variable changes in blood pressure. Convergence of excitatory and inhibitory influences from dorsolateral and ventrolateral stimulating sites in the PAG on to individual cells was also demonstrated. The results are discussed with respect to the role of the ventrolateral PAG in modulating the cardiovascular components of the “defence” response which is integrated by the dorsal PAG.
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  • 53
    ISSN: 1432-1106
    Keywords: Inferior colliculus ; Spinal cord ; Retrograde transport ; Tyrosine hydroxylase ; Glutamate decarboxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The localization and the transmitter phenotype of subparafascicular thalamic nucleus (Spf) neurons projecting to the inferior colliculus (IC) and to the spinal cord (Sp) were studied by using a retrograde fluorescent double labeling technique, and a combined technique of retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD). The cell population of Spf-IC neurons was totally differentiated from that of Spf-Sp neurons which have been reported to be dopaminergic. The former were densely distributed, small to medium sized cells and localized in the central portion of the Spf, while the latter were sparsely distributed, large cells and localized in the marginal portion of the Spf. Spf-IC neurons were completely devoid of TH immunoreactivity and, instead, approximately half of them showed GAD immunoreactivity. From these findings, it is concluded that the Spf is distinctly compartmentalized by the presence at least two separate neuronal subpopulations, which are distinguishable in terms of their cell size, distribution patterns, transmitter phenotypes and trajectories.
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  • 54
    ISSN: 1432-1106
    Keywords: Hyperalgesia ; Peripheral neuropathy ; Nerve histopathology ; Neuropathic pain ; Unmyelinated fibre ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A mononeuropathy, produced by ligation of the sciatic nerve in rats, has recently been proposed as an animal model of experimental pain and pain-related disorders (hyperalgesia and allodynia). We investigated quantitatively the morphological changes in myelinated and unmyelinated fibres of the sciatic nerves 2 weeks after ligation in rats exhibiting allodynia to thermal stimulation. There was a marked reduction in the number of large myelinated fibres distal to the ligature (711 ± 34 compared with 5315 ± 230 in normal nerves). We also found a significant loss of small myelinated fibres (2429 ± 109 compared with 3197 ± 308 in normal nerves), the remaining fibres of this type showing pathological properties. Finally, ultrastructural evidence of damage to unmyelinated fibres was found. The typical pattern of large clusters of normal unmyelinated axons was no longer present within most regions of the nerve. There was a significant reduction in the size of the unmyelinated fibres (0.41 μm ± 0.15 compared with 0.71 μm ± 0.08 in normal nerves), together with a twofold increase in their number per cluster. Hypotheses about the mechanism of thermal allodynia in this pain model therefore must take into account the fact that all fibre classes show pathological changes.
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  • 55
    ISSN: 1432-1106
    Keywords: Frequency modulation ; Intracellular recordings ; Horseradish peroxidase ; Inferior colliculus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The response characteristics to linear frequency sweeps were studied in two groups of FM (frequency modulation) sensitive neurons in the rat inferior colliculus. ‘FM specialized’ cells responded to frequency sweeps but not to pure tones. ‘Mixed’ cells responded to both frequency sweeps and pure tones. FM specialized cells preferred faster and broader sweeps of higher intensity than did mixed cells and were more directionally selective. In addition, FM specialized cells were more sharply tuned to FM velocity and FM range and had longer response latencies. Physiologically identified FM cells stained intracellularly with horseradish peroxidase revealed differences in morphology correlating with the differences in their responses to tones. FM specialized cells had larger dendritic fields, more dendritic branching and more dendritic spines than did mixed cells. The findings are taken as evidence that the two groups of inferior colliculus neurons are both functionally and morphologically distinct.
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  • 56
    ISSN: 1432-1106
    Keywords: Pain ; Nociception ; Spinal cord ; Withdrawal reflexes ; Spinal cord injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spatial organization of the cutaneous input to hindlimb withdrawal reflexes was studied in spinalized, decerebrated, unanesthetized rats. Reflex activity in plantar flexors of the digits, pronators of the foot, dorsiflexors of the digits, and/or the ankle and flexors of the knee was recorded with electromyographic techniques for up to 12 h after spinalization. Graded mechanical (pinch) and thermal stimulation (CO2 laser) of the skin were used. Reflexes were absent (“spinal shock”) during approximately 10–20 min after spinalization. The reflex thresholds for pinch and CO2 laser stimulation then decreased considerably during the following 5–8 h. After this time, even mild pressure (less than 0.1 N/mm2) on the skin was sufficient to evoke a reflex in most muscles. During the period from about 0.5–3 h after spinalization, the nociceptive receptive field of each muscle usually corresponded to the area of the skin withdrawn by the muscle. Maximal responses were evoked from the area of the receptive field maximally withdrawn. During this period, responses to innocuous pinch were evoked mainly from the most sensitive area of the receptive fields. Concomitant with the decrease in reflex thresholds, the nociceptive receptive fields expanded for all muscles, often to include areas of the skin not withdrawn by the muscles. For most muscles, reflexes on tactile stimuli were eventually elicited from the entire receptive fields. The receptive fields for thermonociceptive and mechanonociceptive inputs were similar in most muscles. The interossei muscles were exceptional in that they responded very weakly to thermal stimulation. It is concluded that there are neuronal networks in the spinal cord that translate cutaneous nociceptive and tactile input into a withdrawal. However, the control exerted by descending pathways is necessary to maintain a functionally adequate excitability in these reflex pathways and an appropriate size for their receptive fields.
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  • 57
    ISSN: 1432-1106
    Keywords: Interneuron ; Axo-axonic cell ; Pyramidal cell ; Inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the course of an in vivo intracellular labeling study, a chandelier (axo-axonic) cell was completely filled with biocytin in the CA1 region of the hippocampus. Chandelier cells are known to provide GABAergic terminals exclusively to the axon initial segment of pyramidal cells. The lateral extent and laminar distribution of the dendritic arborization of the chandelier cell was very similar to that of pyramidal cells; the numerous basal and apical dendrites reached the ventricular surface and the hippocampal fissure, respectively. The dendrites, however, had very few spines. The neuron had an asymmetric axonal arbor occupying an elliptical area of 600 by 850 μm in the pyramidal cell layer and stratum oriens, with over three-quarters of the axon projecting to the fimbrial side of the neuron. Counting all clusters of terminals, representing individually innervated axon initial segments, the chandelier cell was estimated to contact 1214 pyramidal cells, a number that exceeds previous estimations, based on Golgi studies, by several-fold. The findings support the view that chandelier cells may control the threshold and/or synchronize large populations of principal cells.
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  • 58
    ISSN: 1432-1106
    Keywords: Taste ; Cortex ; Receptive fields ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Receptive fields (RFs) of 59 cortical taste neurons (35 in the granular insular area, area GI, 21 in the dysgranular insular area, area DI, and 3 in the agranular insular area, area AI) were identified in the oral cavity of the rat. The fraction of the neurons with RFs in the anterior oral cavity only was significantly larger in area GI (74.3%) than in area DI (42.9%). On the other hand, the fraction of neurons with RFs in both the anterior and posterior oral cavity was larger in area DI (42.9%) than in area GI (11.4%). On the whole, it is suggested that area GI is involved in discrimination of several taste stimuli in the oral cavity, whereas in area DI taste information originating from various regions of the oral cavity is integrated. When neurons were classified according to the best stimulus which most excited the neuron among the four basic tastes, different categories of taste neurons had RFs in different parts of the oral cavity. It is suggested that, in either taste area, different categories of taste neurons are involved in different sorts of taste coding. The majority of neurons in both areas had bilateral RFs. In area GI, neurons with RFs on single subpopulations of taste buds were significantly more numerous at the rostral region of the cortex than at the caudal region. There was no such relation between RF types and cortical localization in area DI. Otherwise, topographic representation of the oral cavity by taste neurons on the cortical surface was not obvious. RF features of taste neurons did not differ across layers in either cortical area.
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  • 59
    ISSN: 1432-1106
    Keywords: Taste ; Insular cortex ; Response profile ; Inhibitory response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The responses of 84 taste neurons to stimulation of the oral cavity in rats were examined; most taste neurons were found in either a granular insular area (area GI; n = 55) or dysgranular insular area (DI; n = 25), and the others (n = 4) were in an agranular insular area (area AI). The fraction of neurons responding to only one of the four basic stimuli was significantly larger in area GI than in area DI. When neurons were classified by the stimulus which most excited the neuron among the four basic stimuli, every “best-stimulus category” of neurons was found in both GI and DI areas. Quinine-best and “multistimulus-type” neurons, whose responses to some non-best stimulus exceeded 90% of the maximum, were more numerous in the cortex than in the thalamocortical relay neurons. When responses were plotted against taste stimuli arranged in the order of sucrose, NaCl, HCl, and quinine along the abscissa (taste coordinate), response profiles of taste neurons often showed two peaks. The double-peaked type of response profiles were found in every best-stimulus category of neurons in both areas; though, a significantly large fraction of quinine-best neurons in area GI were of the double-peaked type. Some taste neurons in area GI (n = 21) and in area DI (n = 7) were inhibited by one to two taste stimuli, particularly by the stimuli present next to the best one along the taste coordinate. In correlation profiles — correlation coefficients between sucrose and NaCl and between HCl and quinine — pairs of stimuli which were located next to each other on the taste coordinate were significantly smaller in area GI than in area DI. It is thus highly probable that area GI plays an important role in fine taste discrimination and area DI in integration of taste information.
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