title: Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons.
abstract: Most cortical neurons fire regularly when excited by a constant stimulus. In contrast, irregular-spiking (IS) interneurons are remarkable for the intrinsic variability of their spike timing, which can synchronize amongst IS cells via specific gap junctions. Here, we have studied the biophysical mechanisms of this irregular spiking in mice, and how IS cells fire in the context of synchronous network oscillations. Using patch-clamp recordings, artificial dynamic conductance injection, pharmacological analysis and computational modeling, we show that spike time irregularity is generated by a nonlinear dynamical interaction of voltage-dependent sodium and fast-inactivating potassium channels just below spike threshold, amplifying channel noise. This active irregularity may help IS cells synchronize with each other at gamma range frequencies, while resisting synchronization to lower input frequencies.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Philipe Rf
authors.identifier: 0000-0003-1675-642X
authors.initials: PR
authors.lastname: Mendonça
authors.affiliation: Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.|Centre for Biological Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Mariana
authors.identifier: 0000-0003-2326-4001
authors.initials: M
authors.lastname: Vargas-Caballero
authors.affiliation: Division of Medical Gene Technology, Institute of Experimental Medicine, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Erdélyi
authors.affiliation: Division of Medical Gene Technology, Institute of Experimental Medicine, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ole
authors.identifier: 0000-0002-2258-5455
authors.initials: O
authors.lastname: Paulsen
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Hugh Pc
authors.identifier: 0000-0002-5048-9954
authors.initials: HP
authors.lastname: Robinson
mesh_terms: D000200:Action Potentials; D000818:Animals; D055592:Biophysical Phenomena; D002540:Cerebral Cortex / Q000166:cytology*; D003198:Computer Simulation; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D061566:Voltage-Gated Sodium Channels
keywords: computational biology; cortical interneuron; mouse; neuroscience; spiking irregularity; systems biology; voltage-gated potassium conductance