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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  • dc.contributor.author Otto, Christianeca
  • dc.contributor.author Kovalchuk, Yuryca
  • dc.contributor.author Wolfer, David Paulca
  • dc.contributor.author Gass, Peterca
  • dc.contributor.author Martín, Miguelca
  • dc.contributor.author Zuschratter, Wernerca
  • dc.contributor.author Gröne, Hermann Josefca
  • dc.contributor.author Kellendonk, Christophca
  • dc.contributor.author Tronche, Françoisca
  • dc.contributor.author Maldonado, Rafael, 1961-ca
  • dc.contributor.author Lipp, Hans-Peterca
  • dc.contributor.author Konnerth, Arthurca
  • dc.contributor.author Schütz, Günterca
  • dc.date.accessioned 2012-07-05T06:54:15Z
  • dc.date.available 2012-07-05T06:54:15Z
  • dc.date.issued 2001ca
  • dc.description.abstract 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.
  • dc.description.sponsorship 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.
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Otto C, Kovalchuk Y, Wolfer DP, Gass P, Martin M, Zuschratter W et al. Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient Mice. J Neurosci. 2001;21(15):5520-7. DOI: 10.1523/jneurosci.21-15-05520.2001ca
  • dc.identifier.doi http://dx.doi.org/10.1523/jneurosci.21-15-05520.2001
  • dc.identifier.issn 0270-6474ca
  • dc.identifier.uri http://hdl.handle.net/10230/16668
  • dc.language.iso engca
  • dc.publisher Society for Neuroscienceca
  • dc.relation.ispartof Journal of Neuroscience. 2001;21(15):5520-7
  • dc.rights © 2001, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/21/15/5520ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.keyword PACAP type I receptor
  • dc.subject.keyword Knock-out mice
  • dc.subject.keyword Fear conditioning
  • dc.subject.keyword Synaptic plasticity
  • dc.subject.keyword LTP
  • dc.subject.keyword Mossy fiber
  • dc.subject.other Xarxes neuronals (Neurobiologia)
  • dc.subject.other Neuropèptids
  • dc.title Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient Miceca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersion