Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons.

Philipe Rf Mendonça,Hugh Pc Robinson,Gábor Szabó,Ole Paulsen,Mariana Vargas-Caballero,Ferenc Erdélyi

doi:10.7554/elife.16475

Philipe Rf Mendonça, Hugh Pc Robinson + Show 4 more

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https://doi.org/10.7554/elife.16475

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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.

Highlights

From the Hodgkin and Huxley model onwards, we have a good understanding of the dynamical basis of regular or periodic firing, and of various kinds of burst firing (FitzHugh, 1961; Hindmarsh and Rose, 1984; Hodgkin and Huxley, 1952)
In the cortex of Gad2-green fluorescent protein (GFP) mice, fluorescent cell bodies are concentrated in layer 2, with dendrites concentrated in layers 1 and 2/3 and axons which ramify through the cortical layers (Figure 1a)
In response to a step current stimulus in a whole-cell current-clamp recording, 77% (82/106) of the cells showed a characteristic pattern of action potentials (APs) at irregular intervals, with fairly deep and slow afterhyperpolarizations, often following an initial adaptation phase (Figure 1bi)

Summary

Introduction

From the Hodgkin and Huxley model onwards, we have a good understanding of the dynamical basis of regular or periodic firing, and of various kinds of burst firing (FitzHugh, 1961; Hindmarsh and Rose, 1984; Hodgkin and Huxley, 1952). The nature of intrinsically irregular firing has resisted elucidation, and appears to be a more complex phenomenon. Irregularity of firing in neurons can arise because of fluctuating patterns of synaptic input due to spontaneous activity (Destexhe et al, 2001), or from stochastic fluctuations in the release of transmitter (Ribrault et al, 2011). The cellular mechanisms of such intrinsic irregularity are unknown, though the stochastic gating of the ion channels involved in spike generation seems likely to play a part. Effective chaos in the nonlinear dynamics of the voltage-dependent ion channels involved in spike generation could contribute to irregular patterns of membrane potential (Durstewitz and Gabriel, 2007; Fan and Chay, 1994)

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