Interplay of CaHVA and Ca²⁺-activated K⁺channels affecting firing rate in perineuronal net disruption

Abstract

Perineuronal nets (PNNs) are extracellular matrix structures consisting of proteoglycans crosslinked to hyaluronan. They wrap around subgroups of individual neurons in the brain, primarily parvalbumin positive inhibitory neurons. The nets have been found to affect conductances and activation curves of certain ion channels, including Ca2+-activated K+and high-voltage-activated Ca2+channels. We studied how PNN related parameters affected the firing rate of one-compartment neuron models. We found that the direct effect of the CaHVA current on firing rate was small, while it had a much larger indirect effect on firing rate through initiation of the SK current. Upregulation of the SK conductance similarly had a pronounced effect on the firing rate. The SK currents therefore acted as the main determinant of firing rate out of these two mechanisms. We shifted the CaHVA channel activation by 14.5 mV and increased the SK conductance by a factor of 3.337, consistent with experimental findings on PNN breakdown in the literature. We studied this in nine different models and found a reduction in firing rate in some, but not all, of these models.