NMDA receptors in hippocampal GABAergic synapses and their role in nitric oxide signaling Journal Article


Author(s): Szabadits, Eszter; Cserép, Csaba; Szonyi, András; Fukazawa, Yugo; Shigemoto, Ryuichi; Watanabe, Masahiko; Itohara, Shigeyoshi; Freund, Tamás F; Nyíri, Gábor
Article Title: NMDA receptors in hippocampal GABAergic synapses and their role in nitric oxide signaling
Affiliation
Abstract: GABAergic inhibition plays a central role in the control of pyramidal cell ensemble activities; thus, any signaling mechanism that regulates inhibition is able to fine-tune network patterns. Here, we provide evidence that the retrograde nitric oxide (NO)- cGMP cascade triggered by NMDA receptor (NMDAR) activation plays a role in the control of hippocampal GABAergic transmission in mice. GABAergic synapses express neuronal nitric oxide synthase (nNOS) postsynaptically and NO receptors (NO-sensitive guanylyl cyclase) in the presynaptic terminals. We hypothesized that-similar to glutamatergic synapses-the Ca 2+ transients required to activate nNOS were provided by NMDA receptor activation. Indeed, administration of 5 μm NMDA induced a robust nNOS-dependent cGMP production in GABAergic terminals, selectively in the CA1 and CA3c areas. Furthermore, using preembedding, postembedding, and SDS-digested freeze-fracture replica immunogold labeling, we provided quantitative immunocytochemical evidence that NMDAR subunits GluN1, GluN2A, and GluN2B were present in most somatic GABAergic synapses postsynaptically. These data indicate that NMDARs can modulate hippocampal GABAergic inhibition via NO- cGMP signaling in an activity-dependent manner and that this effect is subregion specific in the mouse hippocampus.
Keywords: Nitric Oxide; n methyl dextro aspartic acid receptor 2B; n methyl dextro aspartic acid receptor; calcium ion; n methyl dextro aspartic acid; cyclic GMP; guanylate cyclase; n methyl dextro aspartic acid receptor 1; n methyl dextro aspartic acid receptor 2A; neuronal nitric oxide synthase
Journal Title: Journal of Neuroscience
Volume: 31
Issue 16
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Date Published: 2011-04-20
Start Page: 5893
End Page: 5904
DOI: 10.1523/JNEUROSCI.5938-10.2011
Open access: no