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Mechanisms of gain control by voltage-gated channels in intrinsically-firing neurons.


Type

Article

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Authors

Patel, Ameera X 
Burdakov, Denis 

Abstract

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems.

Description

This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115431.

Keywords

Calcium Channels, Ion Channel Gating, Membrane Potentials, Models, Neurological, Neurons, Potassium Channels

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

10

Publisher

Public Library of Science (PLoS)
Sponsorship
This work was supported by the Wellcome Trust- and GSK-funded TMAT programme (085686/ Z/08/C, AXP), the University of Cambridge MB/PhD Programme (AXP), the European Research Council (FP7 starting grant to DB) and the UK Medical Research Council (DB, ref: MC\_UP\_1202/2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.