Responses in fast-spiking interneuron firing rates to parameter variations associated with degradation of perineuronal nets

Abstract

The perineuronal nets (PNNs) are sugar coated protein structures that encapsulate certain neurons in the brain, such as parvalbumin positive (PV) inhibitory neurons. As PNNs are theorized to act as a barrier to ion transport, they may effectively increase the membrane charge-separation distance, thereby affecting the membrane capacitance. Tewari et al. (2018) found that degradation of PNNs induced a 25%-50% increase in membrane capacitance cm and a reduction in the firing rates of PV-cells. In the current work, we explore how changes in cm affects the firing rate in a selection of computational neuron models, ranging in complexity from a single compartment Hodgkin-Huxley model to morphologically detailed PV-neuron models. In all models, an increased cm lead to reduced firing, but the experimentally reported increase in cm was not alone sufficient to explain the experimentally reported reduction in firing rate. We therefore hypothesized that PNN degradation in the experiments affected not only cm, but also ionic reversal potentials and ion channel conductances. In simulations, we explored how various model parameters affected the firing rate of the model neurons, and identified which parameter variations in addition to cm that are most likely candidates for explaining the experimentally reported reduction in firing rate.