Desynchronization of neocortical networks by asynchronous release of GABA at autaptic and synaptic contacts from fast-spiking interneurons

Networks of specific inhibitory interneurons regulate principal cell firing in several forms of neocortical activity. fast-spiking (fs) interneurons are potently self-inhibited by gabaergic autaptic transmission,allowing them to precisely control their own firing dynamics and timing. here we show that in fs interneurons,high-frequency trains of action potentials can generate a delayed and prolonged gabaergic self-inhibition due to sustained asynchronous release at fs-cell autapses. asynchronous release of gaba is simultaneously recorded in connected pyramidal (p) neurons. asynchronous and synchronous autaptic release show differential presynaptic ca2+ sensitivity,suggesting that they rely on different ca2+ sensors and/or involve distinct pools of vesicles. in addition,asynchronous release is modulated by the endogenous ca2+ buffer parvalbumin. functionally,asynchronous release decreases fs-cell spike reliability and reduces the ability of p neurons to integrate incoming stimuli into precise firing. since each fs cell contacts many p neurons,asynchronous release from a single interneuron may desynchronize a large portion of the local network and disrupt cortical information processing. © 2010 manseau et al.