Modulation and function of the autaptic connections of layer V fast spiking interneurons in the rat neocortex

Neocortical fast-spiking (FS) basket cells form dense autaptic connections that provide inhibitory GABAergic feedback after each action potential. It has been suggested that these autaptic connections are used because synaptic communication is sensitive to neuromodulation, unlike the voltage-sensitive potassium channels in FS cells. Here we show that layer V FS interneurons form autaptic connections that are largely perisomatic, and without perturbing intracellular Cl- homeostasis, that perisomatic GABAergic currents have a reversal potential of -78 +/- 4 mV. Using variance-mean analysis, we demonstrate that autaptic connections have a mean of 14 release sites (range 4-26) with a quantal amplitude of 101 +/- 16 pA and a probability of release of 0.64 (V(command) = -70 mV, [Ca2+](o) = 2 mm, [Mg2+](o) = 1 mm). We found that autaptic GABA release is sensitive to GABA(B) and muscarinic acetylcholine receptors, but not a range of other classical neuromodulators. Our results indicate that GABA transporters do not regulate FS interneuron autapses, yet autaptically released GABA does not act at GABA(B) or extrasynaptic GABA(A) receptors. This research confirms that the autaptic connections of FS cells are indeed susceptible to modulation, though only via specific GABAergic and cholinergic mechanisms.