Different transmitter transients underlie presynaptic cell type specificity of GABA_(A, slow) and GABA_(A, fast)

摘要

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) 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.