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          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents

ID: 566756.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
The role of NMDAR subtypes and charge transfer during hippocampal LTP induction
Translation of Title:The role of NMDAR subtypes and charge transfer during hippocampal LTP induction
Authors:Berberich, Sven; Jensen, Vidar; Hvalby, Øivind; Seeburg, Peter H.; Köhr, Georg
Date of Publication (YYYY-MM-DD):2007-01-01
Title of Journal:Neuropharmacology
Journal Abbrev.:Neuropharmacology
Issue / Number:1
Start Page:77
End Page:86
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations, such as long−term potentiation of synaptic transmission (LTP). NMDARs are composed of NR1 and NR2 subunits, and NR2 subunit−dependent gating properties of NMDAR subtypes cause dramatic differences in the timing of charge transfer. These postsynaptic temporal profiles are further influenced by the frequency of synaptic activation. Here, we investigated in the CA1 region of hippocampal slices from P28 mice, whether particular NMDAR subtypes are recruited based on NR2 subunit−specific gating following different induction protocols. For high frequency afferent stimulation (HFS), we found that genetic impairment of NR2A or pharmacological block of NR2A− or NR2B−type NMDARs can reduce field LTP. In contrast, when pairing low frequency synaptic stimulation with postsynaptic depolarization (LFS pairing) in single CA1 neurons, pharmacological antagonism of either subtype modestly reduced the charge transfer during LFS pairing without reducing the LTP magnitude. These results indicate that HFS−triggered LTP is induced by more than one NMDAR subtype, whereas a single subtype is sufficient during LFS pairing. Analysis of charge transfer during LFS pairing in 13 different conditions revealed a threshold for LTP induction, which was independent of the NR2 antagonist tested. Thus, at least for LFS pairing, the amount of charge transfer, and thus Ca2+ influx, during LTP induction is a factor more critical than the participation of a particular NMDAR subtype
Free Keywords:Frequency; Temporal signaling; Gene−targeted mouse; NVP−AAM077; Ro25−6981; CP−101,606
Last Change of the Resource (YYYY-MM-DD):--
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
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