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          Institute: MPI für medizinische Forschung     Collection: Jahrbuch 2012     Display Documents



ID: 638164.0, MPI für medizinische Forschung / Jahrbuch 2012
D4 Dopamine Receptors Modulate NR2B NMDA Receptors and LTP in Stratum Oriens of Hippocampal CA1
Translation of Title:D4 Dopamine Receptors Modulate NR2B NMDA Receptors and LTP in Stratum Oriens of Hippocampal CA1
Authors:Herwerth, Marina; Jensen, Vidar; Novak, Martin; Konopka, Withold; Hvalby, Oivind; Köhr, Georg
Language:English
Date of Publication (YYYY-MM-DD):2012-12-01
Title of Journal:Cerebral Cortex
Journal Abbrev.:Cerebral Cortex
Volume:22
Issue / Number:8
Start Page:1786
End Page:1798
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Dopamine plays an important role in synaptic plasticity and learning and is involved in the pathogenesis of various neurological and psychiatric disorders. Here, we reveal staining of dopaminergic fibers in stratum oriens of the mouse hippocampal CA1 region, a finding that is consistent with earlier reports. Furthermore, we examined the effect of dopamine agonists on NMDAR−dependent early long−term potentiation (LTP) (40 min) during γ−aminobutyric acid (GABA)A−mediated blockade. LTP of the AMPA component was strongly reduced in stratum oriens but barely affected in stratum radiatum. This layer−specific effect was caused by D4 receptor activation, which augmented the inactivation of synaptic NMDAR−mediated currents (NMDA EPSCs) during LTP induction through a Ca2+−dependent G−protein−independent mechanism. A similar dopaminergic modulation of both NMDA EPSCs and LTP was also observed in mice constitutively lacking NR2A but was absent in mice lacking NR2B in principal forebrain neurons. Together, these experiments strongly indicate that dopaminergic modulation of early LTP in stratum oriens occurs through NMDARs containing NR2B subunits via D4Rs. Thus, a dopamine hyperfunction in stratum oriens may result in NMDAR hypofunction that could affect both normal and pathological conditions
Free Keywords:L−745,870
PD168077
schizophrenia
SKF38393
stratum radiatum
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie
MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie/Gruppe Georg Köhr
Identifiers:LOCALID:7701
URI:http%3A%2F%2Fcercor.oxfordjournals.org%2Fcontent%2...
URI:http%3A%2F%2Fcercor.oxfordjournals.org%2Fcontent%2...
URI:http%3A%2F%2Fcercor.oxfordjournals.org%2Fcontent%2...
DOI:10.1093%2Fcercor%2Fbhr275
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