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Dysbindin-1 loss compromises NMDAR-dependent synaptic plasticity and contextual fear conditioning.
Glen, W Bailey; Horowitz, Bryant; Carlson, Gregory C; Cannon, Tyrone D; Talbot, Konrad; Jentsch, J David; Lavin, Antonieta.
Afiliação
  • Glen WB; Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Hippocampus ; 24(2): 204-13, 2014 Feb.
Article em En | MEDLINE | ID: mdl-24446171
Genetic variants in DTNBP1 encoding the protein dysbindin-1 have often been associated with schizophrenia and with the cognitive deficits prominent in that disorder. Because impaired function of the hippocampus is thought to play a role in these memory deficits and because NMDAR-dependent synaptic plasticity in this region is a proposed biological substrate for some hippocampal-dependent memory functions in schizophrenia, we hypothesized that reduced dysbindin-1 expression would lead to impairments in NMDAR-dependent synaptic plasticity and in contextual fear conditioning. Acute slices from male mice carrying 0, 1, or 2 null mutant alleles of the Dtnbp1 gene were prepared, and field recordings from the CA1 striatum radiatum were obtained before and after tetanization of Schaffer collaterals of CA3 pyramidal cells. Mice homozygous for the null mutation in Dtnbp1 exhibited significantly reduced NMDAR-dependent synaptic potentiation compared to wild type mice, an effect that could be rescued by bath application of the NMDA receptor coagonist glycine (10 µM). Behavioral testing in adult mice revealed deficits in hippocampal memory processes. Homozygous null mice exhibited lower conditional freezing, without a change in the response to shock itself, indicative of a learning and memory deficit. Taken together, these results indicate that a loss of dysbindin-1 impairs hippocampal plasticity which may, in part, explain the role dysbindin-1 plays in the cognitive impairments of schizophrenia.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Proteínas de Transporte / Receptores de N-Metil-D-Aspartato / Potenciação de Longa Duração / Condicionamento Psicológico / Medo Limite: Animals Idioma: En Revista: Hippocampus Assunto da revista: CEREBRO Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Proteínas de Transporte / Receptores de N-Metil-D-Aspartato / Potenciação de Longa Duração / Condicionamento Psicológico / Medo Limite: Animals Idioma: En Revista: Hippocampus Assunto da revista: CEREBRO Ano de publicação: 2014 Tipo de documento: Article