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

Abstract

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