title: Hippocampal GABAergic synapses possess the molecular machinery for retrograde nitric oxide signaling.
abstract: Nitric oxide (NO) plays an important role in synaptic plasticity as a retrograde messenger at glutamatergic synapses. Here we describe that, in hippocampal pyramidal cells, neuronal nitric oxide synthase (nNOS) is also associated with the postsynaptic active zones of GABAergic symmetrical synapses terminating on their somata, dendrites, and axon initial segments in both mice and rats. The NO receptor nitric oxide-sensitive guanylyl cyclase (NOsGC) is present in the brain in two functional subunit compositions: alpha1beta1 and alpha2beta1. The beta1 subunit is expressed in both pyramidal cells and interneurons in the hippocampus. Using immunohistochemistry and in situ hybridization methods, we describe that the alpha1 subunit is detectable only in interneurons, which are always positive for beta1 subunit as well; however, pyramidal cells are labeled only for beta1 and alpha2 subunits. With double-immunofluorescent staining, we also found that most cholecystokinin- and parvalbumin-positive and smaller proportion of the somatostatin- and nNOS-positive interneurons are alpha1 subunit positive. We also found that the alpha1 subunit is present in parvalbumin- and cholecystokinin-positive interneuron terminals that establish synapses on somata, dendrites, or axon initial segments. Our results demonstrate that NOsGC, composed of alpha1beta1 subunits, is selectively expressed in different types of interneurons and is present in their presynaptic GABAergic terminals, in which it may serve as a receptor for NO produced postsynaptically by nNOS in the very same synapse.
authors.affiliation: Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Szabadits
authors.forename: Csaba
authors.initials: C
authors.lastname: Cserép
authors.forename: Anikó
authors.initials: A
authors.lastname: Ludányi
authors.forename: István
authors.initials: I
authors.lastname: Katona
authors.forename: Javier
authors.initials: J
authors.lastname: Gracia-Llanes
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
authors.forename: Gábor
authors.initials: G
authors.lastname: Nyíri
mesh_terms: D000818:Animals; D006162:Guanylate Cyclase / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D013569:Synapses / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D052248:Nitric Oxide Synthase Type I; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase