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The role of NMDAR subtypes and charge transfer during hippocampal LTP induction.
Neuropharmacology. 2007 Jan; 52(1):77-86.N

Abstract

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.

Authors+Show Affiliations

Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16901514

Citation

Berberich, Sven, et al. "The Role of NMDAR Subtypes and Charge Transfer During Hippocampal LTP Induction." Neuropharmacology, vol. 52, no. 1, 2007, pp. 77-86.
Berberich S, Jensen V, Hvalby Ø, et al. The role of NMDAR subtypes and charge transfer during hippocampal LTP induction. Neuropharmacology. 2007;52(1):77-86.
Berberich, S., Jensen, V., Hvalby, Ø., Seeburg, P. H., & Köhr, G. (2007). The role of NMDAR subtypes and charge transfer during hippocampal LTP induction. Neuropharmacology, 52(1), 77-86.
Berberich S, et al. The Role of NMDAR Subtypes and Charge Transfer During Hippocampal LTP Induction. Neuropharmacology. 2007;52(1):77-86. PubMed PMID: 16901514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of NMDAR subtypes and charge transfer during hippocampal LTP induction. AU - Berberich,Sven, AU - Jensen,Vidar, AU - Hvalby,Øivind, AU - Seeburg,Peter H, AU - Köhr,Georg, Y1 - 2006/08/09/ PY - 2006/05/21/received PY - 2006/07/10/revised PY - 2006/07/12/accepted PY - 2006/8/12/pubmed PY - 2007/3/3/medline PY - 2006/8/12/entrez SP - 77 EP - 86 JF - Neuropharmacology JO - Neuropharmacology VL - 52 IS - 1 N2 - 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. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/16901514/The_role_of_NMDAR_subtypes_and_charge_transfer_during_hippocampal_LTP_induction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00230-9 DB - PRIME DP - Unbound Medicine ER -