desynchronization of neocortical networks by asynchronous release of gaba at autaptic and synaptic contacts from fast-spiking interneurons失调的皮层网络异步释放gaba在autaptic从fast-spiking中间神经元和突触联系.pdfVIP

Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons ´ ´ 1 1 ´ 1 2 3 Frederic Manseau , Silvia Marinelli , Pablo Mendez , Beat Schwaller , David A. Prince , John R. 3 1 Huguenard , Alberto Bacci * 1 European Brain Research Institute, Rome, Italy, 2 Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland, 3 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, United States of America Abstract 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 neur