TY - JOUR T1 - NMDA Receptors in Hippocampal GABAergic Synapses and Their Role in Nitric Oxide Signaling JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5893 LP - 5904 DO - 10.1523/JNEUROSCI.5938-10.2011 VL - 31 IS - 16 AU - Eszter Szabadits AU - Csaba Cserép AU - András Szőnyi AU - Yugo Fukazawa AU - Ryuichi Shigemoto AU - Masahiko Watanabe AU - Shigeyoshi Itohara AU - Tamás F. Freund AU - Gábor Nyiri Y1 - 2011/04/20 UR - http://www.jneurosci.org/content/31/16/5893.abstract N2 - 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 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 via NO–cGMP signaling in an activity-dependent manner and that this effect is subregion specific in the mouse hippocampus. ER -