Different transmitter transients underlie presynaptic cell type specificity of GABAA,slow and GABAA,fast

Phasic (synaptic) and tonic (extrasynaptic) inhibition represent the two most fundamental forms of GABA(A) receptor-mediated transmission. Inhibitory postsynaptic currents (IPSCs) generated by GABAA receptors are typically extremely rapid synaptic events that do not last beyond a few milliseconds. Although unusually slow GABAA 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 GABAA,Slow IPSCs originate from a specialized interneuron called neurogliaform cells. Compared with classical GABAA,fast IPSCs evoked by basket cells, single spikes in neurogliaform cells evoke extraordinarily prolonged GABAA responses that display tight regulation by transporters, low peak GABA concentration, unusual benzodiazepine modulation, and spillover. These results reveal a form of GABAA receptor mediated communication by a dedicated cell type that produces slow ionotropic responses with properties intermediate between phasic and tonic inhibition.