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NMDA receptor activation enhances inhibitory GABAergic transmission onto hippocampal pyramidal neurons via presynaptic and postsynaptic mechanisms.
J Neurophysiol 2011; 105(6):2897-906JN

Abstract

N-methyl-D-aspartate (NMDA) receptors (NMDARs) are implicated in synaptic plasticity and modulation of glutamatergic excitatory transmission. Effect of NMDAR activation on inhibitory GABAergic transmission remains largely unknown. Here, we report that a brief application of NMDA could induce two distinct actions in CA1 pyramidal neurons in mouse hippocampal slices: 1) an inward current attributed to activation of postsynaptic NMDARs; and 2) fast phasic synaptic currents, namely spontaneous inhibitory postsynaptic currents (sIPSCs), mediated by GABA(A) receptors in pyramidal neurons. The mean amplitude of sIPSCs was also increased by NMDA. This profound increase in the sIPSC frequency and amplitude was markedly suppressed by the sodium channel blocker TTX, whereas the frequency and mean amplitude of miniature IPSCs were not significantly affected by NMDA, suggesting that NMDA elicits repetitive firing in GABAergic interneurons, thereby leading to GABA release from multiple synaptic sites of single GABAergic axons. We found that the NMDAR open-channel blocker MK-801 injected into recorded pyramidal neurons suppressed the NMDA-induced increase of sIPSCs, which raises the possibility that the firing of interneurons may not be the sole factor and certain retrograde messengers may also be involved in the NMDA-mediated enhancement of GABAergic transmission. Our results from pharmacological tests suggest that the nitric oxide signaling pathway is mobilized by NMDAR activation in CA1 pyramidal neurons, which in turn retrogradely facilitates GABA release from the presynaptic terminals. Thus NMDARs at glutamatergic synapses on both CA1 pyramidal neurons and interneurons appear to exert feedback and feedforward inhibition for determining the spike timing of the hippocampal microcircuit.

Authors+Show Affiliations

Department of Neurophysiology, Kagawa School of Pharmaceutical Sciences and Institute of Neuroscience, Tokushima Bunri University, Kagawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21471392

Citation

Xue, Jiu-Gang, et al. "NMDA Receptor Activation Enhances Inhibitory GABAergic Transmission Onto Hippocampal Pyramidal Neurons Via Presynaptic and Postsynaptic Mechanisms." Journal of Neurophysiology, vol. 105, no. 6, 2011, pp. 2897-906.
Xue JG, Masuoka T, Gong XD, et al. NMDA receptor activation enhances inhibitory GABAergic transmission onto hippocampal pyramidal neurons via presynaptic and postsynaptic mechanisms. J Neurophysiol. 2011;105(6):2897-906.
Xue, J. G., Masuoka, T., Gong, X. D., Chen, K. S., Yanagawa, Y., Law, S. K., & Konishi, S. (2011). NMDA receptor activation enhances inhibitory GABAergic transmission onto hippocampal pyramidal neurons via presynaptic and postsynaptic mechanisms. Journal of Neurophysiology, 105(6), pp. 2897-906. doi:10.1152/jn.00287.2010.
Xue JG, et al. NMDA Receptor Activation Enhances Inhibitory GABAergic Transmission Onto Hippocampal Pyramidal Neurons Via Presynaptic and Postsynaptic Mechanisms. J Neurophysiol. 2011;105(6):2897-906. PubMed PMID: 21471392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA receptor activation enhances inhibitory GABAergic transmission onto hippocampal pyramidal neurons via presynaptic and postsynaptic mechanisms. AU - Xue,Jiu-Gang, AU - Masuoka,Takayoshi, AU - Gong,Xian-Di, AU - Chen,Ken-Shiung, AU - Yanagawa,Yuchio, AU - Law,S K Alex, AU - Konishi,Shiro, Y1 - 2011/04/06/ PY - 2011/4/8/entrez PY - 2011/4/8/pubmed PY - 2011/10/15/medline SP - 2897 EP - 906 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 105 IS - 6 N2 - N-methyl-D-aspartate (NMDA) receptors (NMDARs) are implicated in synaptic plasticity and modulation of glutamatergic excitatory transmission. Effect of NMDAR activation on inhibitory GABAergic transmission remains largely unknown. Here, we report that a brief application of NMDA could induce two distinct actions in CA1 pyramidal neurons in mouse hippocampal slices: 1) an inward current attributed to activation of postsynaptic NMDARs; and 2) fast phasic synaptic currents, namely spontaneous inhibitory postsynaptic currents (sIPSCs), mediated by GABA(A) receptors in pyramidal neurons. The mean amplitude of sIPSCs was also increased by NMDA. This profound increase in the sIPSC frequency and amplitude was markedly suppressed by the sodium channel blocker TTX, whereas the frequency and mean amplitude of miniature IPSCs were not significantly affected by NMDA, suggesting that NMDA elicits repetitive firing in GABAergic interneurons, thereby leading to GABA release from multiple synaptic sites of single GABAergic axons. We found that the NMDAR open-channel blocker MK-801 injected into recorded pyramidal neurons suppressed the NMDA-induced increase of sIPSCs, which raises the possibility that the firing of interneurons may not be the sole factor and certain retrograde messengers may also be involved in the NMDA-mediated enhancement of GABAergic transmission. Our results from pharmacological tests suggest that the nitric oxide signaling pathway is mobilized by NMDAR activation in CA1 pyramidal neurons, which in turn retrogradely facilitates GABA release from the presynaptic terminals. Thus NMDARs at glutamatergic synapses on both CA1 pyramidal neurons and interneurons appear to exert feedback and feedforward inhibition for determining the spike timing of the hippocampal microcircuit. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/21471392/NMDA_receptor_activation_enhances_inhibitory_GABAergic_transmission_onto_hippocampal_pyramidal_neurons_via_presynaptic_and_postsynaptic_mechanisms_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00287.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -