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.
Highlights
The activity of a neuron is driven by barrages of synaptic inputs
We demonstrate how the gain control effects of inhibition depend on the A-type Potassium current
We identify a novel role for A-type voltage-gated potassium current in determining whether inhibition acts in a subtractive or divisive manner
Summary
Synaptic inputs are classified as either excitatory (those that promote spike generation) and inhibitory (those that impede spike generation). The interplay between these two “opposing” inputs influences how neurons process and transmit information in the brain. Inhibition is said to be subtractive if it reduces the firing activity of a neuron by (roughly) a constant amount, regardless of the strength or amount of synaptic excitation. Inhibition is said to be divisive if it reduces the firing activity of a neuron by an amount that is (roughly) proportional to the neuron’s firing rate We illustrate this distinction, by showing output firing rate of a neuron as a function of the rate of its excitatory inputs (not actual data)
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