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.