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 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.
Szabadics
János
J
Department of Anatomy and Neurobiology, University of California, 193 Irvine Hall, Irvine, CA 92697, USA.
Tamás
Gábor
G
Soltesz
Ivan
I
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D018755:GABA Agonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D000077334:Zolpidem