Different transmitter transients underlie presynaptic cell type specificity of GAB[A.sub.A, slow] and GAB[A.sub.A, fast]

Phasic (synaptic) and tonic (extrasynaptic) inhibition represent the two most fundamental forms of GAB[A.sub.A] receptor-mediated transmission. Inhibitory postsynaptic currents (IPSCs) generated by GAB[A.sub.A] receptors are typically extremely rapid synaptic events that do not last beyond a few milliseconds. Although unusually slow GAB[A.sub.A] IPSCs, lasting for tens of milliseconds, have been observed in recordings of spontaneous events, their origin and mechanisms are not known. We show that neocortical GAB[A.sub.A,slow] IPSCs originate from a specialized interneuron called neurogliaform cells. Compared with classical GAB[A.sub.A, fast] IPSCS evoked by basket cells, single spikes in neurogliaform cells evoke extraordinarily prolonged GAB[A.sub.A] responses that display tight regulation by transporters, low peak GABA concentration, unusual benzodiazepine modulation, and spillover. These results reveal a form of GAB[A.sub.A] receptor mediated communication by a dedicated cell type that produces slow ionotropic responses with properties intermediate between phasic and tonic inhibition. inhibition | neocortex | neurogliaform cell