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  • 1
    Keywords: brain ; Germany ; LONG-TERM ; GENE ; PROTEIN ; transcription ; TRANSCRIPTION FACTOR ; REDUCTION ; WATER ; MEMORY ; FORM ; CAMP ; CELL-SURVIVAL ; conditioned taste aversion ; CONDITIONED TASTE-AVERSION ; CREB ; DEFICITS ; DELETION ; ELEMENT ; ELEMENT-BINDING PROTEIN ; ELEMENT-BINDING-PROTEIN ; fear conditioning ; hippocampus ; ISOFORM ; ISOFORMS ; knockout ; LATE-PHASE ; learning ; LONG-TERM POTENTIATION ; LTD ; LTP ; MAP KINASE ; MOUSE ; MOUSE-BRAIN ; MUTANT ; NERVOUS-SYSTEM ; NO ; PERFORMANCE ; PROBE ; RESPONSE ELEMENT ; score ; STAGE ; synaptic plasticity ; TARGETED MUTATION ; TRANSCRIPTION FACTORS ; TRANSGENIC MICE ; TRIAL ; TRIALS ; WATER MAZE
    Abstract: Previous studies addressing the role of the transcription factor cAMP response element-binding protein (CREB) in mammalian long-term synaptic plasticity and memory by gene targeting were compromised by incomplete deletion of the CREB isoforms. Therefore, we generated conditional knock-out strains with a marked reduction or complete deletion of all CREB isoforms in the hippocampus. In these strains, no deficits could be detected in lasting forms of hippocampal long-term potentiation (LTP) and long-term depression (LTD). When tested for hippocampus-dependent learning, mutants showed normal context-dependent fear conditioning. Water maze learning was impaired during the early stages, but many mutants showed satisfactory scores in probe trials thought to measure hippocampus-dependent spatial memory. However, conditioned taste aversion learning, a putatively hippocampus-independent memory test, was markedly impaired. Our data indicate that in the adult mouse brain, loss of CREB neither prevents learning nor substantially affects performance in some hippocampus-dependent tasks. Furthermore, it spares LTP and LTD in paradigms that are sensitive enough to detect deficits in other mutants. This implies either a species-specific or regionally restricted role of CREB in the brain and/or a compensatory upregulation of the cAMP response element modulator (CREM) and other as yet unidentified transcription factors
    Type of Publication: Journal article published
    PubMed ID: 12867515
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  • 2
    Keywords: brain ; RECEPTOR ; EXPRESSION ; Germany ; DISEASE ; GENE ; MICE ; RATS ; MEMORY ; hippocampus ; MOUSE ; synaptic plasticity ; UP-REGULATION ; STRESS ; BEHAVIOR ; RE ; NEUROENDOCRINE ; LEVEL ; LOSSES ; BLOCKADE ; ANTAGONISTS ; ADULT MICE ; GLUCOCORTICOID-RECEPTORS ; PITUITARY-ADRENOCORTICAL AXIS
    Abstract: Corticosteroid action in the brain is mediated by the mineralocorticoid (MR) and the glucocorticoid (GR) receptor. Disturbances in MR- and GR-mediated effects are thought to impair cognition, behavior, and endocrine control. To assess the function of the limbic MR in these processes, we inactivated the MR gene in the forebrain of the mouse using the Cre/loxP-recombination system. We screened the mice with a limbic MR deficiency in various learning and exploration tests. The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy. They exhibit a hyperreactivity toward a novel object but normal anxiety-like behavior. The behavioral changes are associated with abnormalities of the mossy fiber projection and an up-regulation of GR expression in the hippocampus. Adult mutant mice show normal corticosterone levels at circadian trough and peak. This genetic model provides important information about the consequences of a permanently altered balance between limbic MR and GR, with implications for stress-related neuroendocrine and neuropsychiatric diseases
    Type of Publication: Journal article published
    PubMed ID: 16368758
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  • 3
    ISSN: 0196-9781
    Keywords: Memory ; Substance P ; Systemic administration
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1106
    Keywords: Ventromedial thalamus ; Superior colliculus ; Apomorphine ; Muscimol ; Metenkephalin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unilateral destruction of the ventromedial thalamus (VMT) with a radiofrequency lesion attenuated turning induced by injection of muscimol (40 ng/0.4 μl) but not of a metenkephalin-analogue (DAME; 2.5 μg/0.4 μl) into the substantia nigra, pars reticulata (SNR). Unilateral lesions in the deep layers of the superior colliculus (DLSC) attenuated both muscimol- and DAME-induced turning. Lesions in the DLSC but not in the VMT blocked the sensitization of the perioral biting reflex by injection of muscimol or DAME into the SNR on the same side of the lesion. When injected with apomorphine (0.5 mg/kg) all rats with lesions turned ipsiversive to the lesion side and reacted to tactile stimulation of the perioral area on both sides with orienting towards and then biting into the stimulus probe.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the present study we further investigate functions of the neural cell adhesion molecule (NCAM) in the mature central nervous system and its implications for animal behaviour. To this end we generated transgenic mice expressing the major NCAM isoform with the largest cytoplasmic domain, NCAM180, under control of a promoter for the small form neurofilament gene. Transgenic mice were also bred with mice deficient in endogenous NCAM (Ncam–/– mice) so that effects of NCAM180 could be analysed in the presence and absence of endogenous NCAM. While overexpression of transgenic NCAM180 was without apparent behavioural or morphological effect, its expression in Ncam–/– mice counteracted NCAM ablation-induced aggressive, anxiety-like and antidepressant-like behaviour. It furthermore prevented a hypersensitivity of Ncam–/– mice to the anxiolytic serotonin1A (5-HT1A) receptor agonist buspirone. Such recovery of emotional behaviour and behavioural 5-HT1A response occurred in spite of misdevelopment of the olfactory bulb and hippocampus that is characteristic of Ncam–/– mice, and without an apparent change in the expression of 5-HT1A binding sites in the brain. Hippocampus- and amygdala-dependent learning, though disturbed in Ncam–/– mice, remained unaffected by the transgenic NCAM180. We suggest an involvement of NCAM180-mediated cell recognition processes in the serotonergic modulation of emotional behaviour in adult mice.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Four separate cohorts of rats were employed to examine the effects of cytotoxic retrohippocampal lesions in four spatial memory tasks which are known to be sensitive to direct hippocampal damage and/or fornix-fimbria lesions in the rat. Selective retrohippocampal lesions were made by means of multiple intracerebral infusions of NMDA centred on the entorhinal cortex bilaterally. Cell damage typically extended from the lateral entorhinal area to the distal ventral subiculum. Experiment 1 demonstrated that retrohippocampal lesions spared the acquisition of a reference memory task in the Morris water maze, in which the animals learned to escape from the water by swimming to a submerged platform in a fixed location. In the subsequent transfer test, when the escape platform was removed, rats with retrohippocampal lesions tended to spend less time searching in the appropriate quadrant compared to controls. Experiment 2 demonstrated that the lesions also spared the acquisition of a working memory version of the water maze task in which the location of the escape platform was varied between days. In experiment 3, both reference and working memory were assessed using an eight-arm radial maze in which the same four arms were constantly baited between trials. In the initial acquisition, reference memory but not working memory was affected by the lesions. During subsequent reversal learning in which previously baited arms were now no longer baited and vice versa, lesioned animals made significantly more reference memory errors as well as working memory errors. In experiment 4, spatial working memory was assessed in a delayed matching-to-position task conducted in a two-lever operant chamber. There was no evidence for any impairment in rats with retrohippocampal lesions in this task. The present study demonstrated that unlike direct hippocampal damage, retrohippocampal cell loss did not lead to a general impairment in spatial learning, implying that the integrity of the retrohippocampus and/or its interconnection with the hippocampal formation is not critical for normal hippocampal-dependent spatial learning and memory. This outcome is surprising for a number of current hippocampal theories, and suggests that other cortical as well as subcortical inputs to the hippocampus might be of more importance, and further raises the question regarding the functional significance of the retrohippocampal region.Introduction
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mice deficient for the neural cell adhesion molecule (NCAM) show morphological and behavioural abnormalities in the adult form, including a reduced size of the olfactory bulb, reduced exploratory behaviour, and deficits in spatial learning. Here we report increased aggressive behaviour of both homozygous (NCAM -/–) and heterozygous (NCAM +/–) male mutant mice towards an unfamiliar male intruding into their home cage. While plasma testosterone concentrations did not differ between genotypes before or after behavioural testing, corticosterone levels were higher in mutant residents than in wild-type (NCAM +/+) residents 30 min after encountering the intruder. Levels of c-fos mRNA, analysed to monitor neuronal activation, were similar in primary output structures of the olfactory bulb in NCAM-deficient and NCAM +/+ mice, but were increased in brain areas of the limbic system in both NCAM –/– and NCAM +/– mutant mice after the behavioural test. These results indicate that abnormalities in social behaviour correlate with enhanced neuronal activity in limbic brain areas and result in increased social stress in NCAM-deficient mice.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 55 (1999), S. 575-592 
    ISSN: 1420-9071
    Keywords: Key words. Neuronal plasticity; consolidation; long-term memory; protein synthesis; gene transcription.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. On a cellular level, formation of memory is based on a selective change in synaptic efficacy that is both fast and, in case of important information, long-lasting. Rapidity of cellular changes is achieved by modifying preexisting synaptic molecules (receptors, ion channels), which instantaneously alters the efficacy of synaptic transmission. Endurance, that is the formation of long-term memory (LTM), is based on transient and perhaps also long-lasting changes in protein synthesis. A number of different methods exist to interfere with the synthesis of specific proteins or proteins in general. Other methods, in turn, help to identify proteins whose synthesis is changed following learning. These mostly molecular methods are briefly described in the present review. Their successful application in a variety of memory paradigms in invertebrates and vertebrates is illustrated. The data support the importance of selective changes in gene expression for LTM. Proteins newly synthesized during memory consolidation are likely to contribute to restructuring processes at the synapse, altering the efficiency of transmission beyond the scope of STM. Increased or, less often, decreased synthesis of proteins appears during specific time windows following learning. Recent evidence supports older data suggesting that two or even more waves of protein synthesis exist during the consolidation period. It is expected that the new molecular methods will help to identify and characterize molecules whose expression changes during LTM formation even in complex vertebrate learning paradigms.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-899X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0163-1047
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Psychology
    Type of Medium: Electronic Resource
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