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.
Highlights
Gain control is a central unsolved problem in the biophysics of neural computation
We found that increases in the G ion of all voltage-gated K+ channels—the A-type channel (IA), the delayed-rectifier K+ channel (IKd), and the Ca2+-activated channel (IKCa)—caused a reduction in gain (Fig. 1)
The biological significance of gain control from changes in maximal conductances Our results demonstrate that an increase in the maximal specific conductance (G ion) of voltagegated K+ channels including the A-type (IA), delayed-rectifier (IKd) and Ca2+-activated (IKCa)
Summary
The ability of neurons to modulate gain is a fundamental feature of neural information processing [1, 2], yet our understanding of the underlying biophysical mechanisms is currently limited. Factors that can effect a shift from a neuron’s tuning curve (the baseline input-output relationship) to another, modulating the gain, may critically underlie many neurophysiological and pathological neural processes. Understanding these factors is critical for understanding brain function [1, 4]
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