Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons |
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Authors: | Frédéric Manseau Silvia Marinelli Pablo Méndez Beat Schwaller David A. Prince John R. Huguenard Alberto Bacci |
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Affiliation: | 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;Northwestern University, United States of America |
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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 neurons, asynchronous release from a single interneuron may desynchronize a large portion of the local network and disrupt cortical information processing. |
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