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Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition.

ABSTRACT: Neurons process and convey information by transforming barrages of synaptic inputs into spiking activity. Synaptic inhibition typically suppresses the output firing activity of a neuron, and is commonly classified as having a subtractive or divisive effect on a neuron's output firing activity. Subtractive inhibition can narrow the range of inputs that evoke spiking activity by eliminating responses to non-preferred inputs. Divisive inhibition is a form of gain control: it modifies firing rates while preserving the range of inputs that evoke firing activity. Since these two "modes" of inhibition have distinct impacts on neural coding, it is important to understand the biophysical mechanisms that distinguish these response profiles. In this study, we use simulations and mathematical analysis of a neuron model to find the specific conditions (parameter sets) for which inhibitory inputs have subtractive or divisive effects. Significantly, we identify a novel role for the A-type Potassium current (IA). In our model, this fast-activating, slowly-inactivating outward current acts as a switch between subtractive and divisive inhibition. In particular, if IA is strong (large maximal conductance) and fast (activates on a time-scale similar to spike initiation), then inhibition has a subtractive effect on neural firing. In contrast, if IA is weak or insufficiently fast-activating, then inhibition has a divisive effect on neural firing. We explain these findings using dynamical systems methods (plane analysis and fast-slow dissection) to define how a spike threshold condition depends on synaptic inputs and IA. Our findings suggest that neurons can "self-regulate" the gain control effects of inhibition via combinations of synaptic plasticity and/or modulation of the conductance and kinetics of A-type Potassium channels. This novel role for IA would add flexibility to neurons and networks, and may relate to recent observations of divisive inhibitory effects on neurons in the nucleus of the solitary tract.

SUBMITTER: Goldwyn JH

PROVIDER: S-EPMC6053252 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition.

Goldwyn Joshua H JH Slabe Bradley R BR Travers Joseph B JB Terman David D

PLoS computational biology 20180709 7

Neurons process and convey information by transforming barrages of synaptic inputs into spiking activity. Synaptic inhibition typically suppresses the output firing activity of a neuron, and is commonly classified as having a subtractive or divisive effect on a neuron's output firing activity. Subtractive inhibition can narrow the range of inputs that evoke spiking activity by eliminating responses to non-preferred inputs. Divisive inhibition is a form of gain control: it modifies firing rates w ...[more]

PMID: 29985917

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Project description:Phasic neurons typically fire only for a fast-rising input, say at the onset of a step current, but not for steady or slow inputs, a property associated with type III excitability. Phasic neurons can show extraordinary temporal precision for phase locking and coincidence detection. Exemplars are found in the auditory brain stem where precise timing is used in sound localization. Phasicness at the cellular level arises from a dynamic, voltage-gated, negative feedback that can be recruited subthreshold, preventing the neuron from reaching spike threshold if the voltage does not rise fast enough. We consider two mechanisms for phasicness: a low threshold potassium current (subtractive mechanism) and a sodium current with subthreshold inactivation (divisive mechanism). We develop and analyze three reduced models with either divisive or subtractive mechanisms or both to gain insight into the dynamical mechanisms for the potentially high temporal precision of type III-excitable neurons. We compare their firing properties and performance for a range of stimuli. The models have characteristic non-monotonic input-output relations, firing rate vs. input intensity, for either stochastic current injection or Poisson-timed excitatory synaptic conductance trains. We assess performance according to precision of phase-locking and coincidence detection by the models' responses to repetitive packets of unitary excitatory synaptic inputs with more or less temporal coherence. We find that each mechanism contributes features but best performance is attained if both are present. The subtractive mechanism confers extraordinary precision for phase locking and coincidence detection but only within a restricted parameter range when the divisive mechanism of sodium inactivation is inoperative. The divisive mechanism guarantees robustness of phasic properties, without compromising excitability, although with somewhat less precision. Finally, we demonstrate that brief transient inhibition if properly timed can enhance the reliability of firing.

Dataset Information

Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition.

Publications

Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition.

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