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- Title
NMDA Receptors in Hippocampal GABAergic Synapses and Their Role in Nitric Oxide Signaling.
- Authors
Szabadits, Eszter; Cserép, Csaba; Szõnyi, András; Fukazawa, Yugo; Shigemoto, Ryuichi; Watanabe, Masahiko; Itohara, Shigeyoshi; Freund, Tamás F.; Nyiri, Gábor
- 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 NMDAreceptor(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 Ca2+ 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 viaNO-cGMPsignaling in an activity-dependent manner and that this effect is subregion specific in the mouse hippocampus.
- Subjects
NITRIC oxide; NEURAL circuitry; ACETOLACTATE synthase; IMMUNOGOLD labeling; LABORATORY mice; GABA
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 16, p5893
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5938-10.2011