title: Astrocytic iNOS-dependent enhancement of synaptic release in mouse neocortex.
abstract: Nitric oxide (NO) has been recognized as an atypical neuronal messenger affecting synaptic transmission, but its cellular source has remained unresolved as the neuronal NO synthase isoform (nNOS) in brain areas such as the neocortex is expressed only by a small subset of inhibitory neurons. The involvement of the glial NOS isoform (iNOS) in modulating neuronal activity has been largely ignored because it has been accepted that this enzyme is regulated by gene induction following detrimental stimuli. Using acute brain slices from mouse neocortex and electrophysiology, we found that selective inhibition of iNOS reduced both spontaneous and evoked synaptic release. Moreover, iNOS inhibition partially prevented and reversed the potentiation of excitatory synapses in layer 2/3 pyramidal neurons. NOS enzymatic assay confirmed a small but reliable Ca(2+)-independent activity fraction, consistent with the existence of functioning iNOS in the tissue. Together these data point to astrocytes as a source for the nitrosative regulation of synaptic release in the neocortex.
authors.affiliation: Dept. of Physiology, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Buskila
authors.forename: Yael
authors.initials: Y
authors.lastname: Amitai
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D019579:Neocortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II