Títol:
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Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient Mice
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Autor/a:
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Otto, Christiane; Kovalchuk, Yury; Wolfer, David Paul; Gass, Peter; Martín, Miguel; Zuschratter, Werner; Gröne, Hermann Josef; Kellendonk, Christoph; Tronche, François; Maldonado, Rafael, 1961-; Lipp, Hans-Peter; Konnerth, Arthur; Schütz, Günter
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Abstract:
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The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PAC1) is a G-protein-coupled receptor binding the strongly conserved neuropeptide PACAP with 1000-fold higher affinity than the related peptide vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in neuronal differentiation and synaptic plasticity. To gain further insight into the biological significance of PAC1-mediated signaling in vivo, we generated two different mutant mouse strains, harboring either a complete or a forebrain-specific inactivation of PAC1. Mutants from both strains show a deficit in contextual fear conditioning, a hippocampus-dependent associative learning paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling declarative learning such as the Morris water maze or the social transmission of food preference are observed. At the cellular level, the deficit in hippocampus-dependent associative learning is accompanied by an impairment of mossy fiber long-term potentiation (LTP). Because the hippocampal expression of PAC1 is restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated signaling at the mossy fiber synapse is involved in both LTP and hippocampus-dependent associative learning. |
Abstract:
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This work was supported by the European Commission, the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, the Bundesministerium fü ̈r Bildung und Forschung, and the Volkswagenstiftung. |
Matèries:
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-Xarxes neuronals (Neurobiologia) -Neuropèptids -PACAP type I receptor -Knock-out mice -Fear conditioning -Synaptic plasticity -LTP -Mossy fiber |
Drets:
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(c) 2001, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/21/15/5520 |
Tipus de document:
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Article Article - Versió publicada |
Publicat per:
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Society for Neuroscience
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