Kv7 channels regulate pairwise spiking covariability in health and disease.
Low-threshold M currents are mediated by the Kv7 family of potassium channels. Kv7 channels are important regulators of spiking activity, having a direct influence on the firing rate, spike time variability, and filter properties of neurons. How Kv7 channels affect the joint spiking activity of populations of neurons is an important and open area of study. Using a combination of computational simulations and analytic calculations, we show that the activation of Kv7 conductances reduces the covariability between spike trains of pairs of neurons driven by common inputs. This reduction is beyond that explained by the lowering of firing rates and involves an active cancellation of common fluctuations in the membrane potentials of the cell pair. Our theory shows that the excess covariance reduction is due to a Kv7-induced shift from low-pass to band-pass filtering of the single neuron spike train response. Dysfunction of Kv7 conductances is related to a number of neurological diseases characterized by both elevated firing rates and increased network-wide correlations. We show how changes in the activation or strength of Kv7 conductances give rise to excess correlations that cannot be compensated for by synaptic scaling or homeostatic modulation of passive membrane properties. In contrast, modulation of Kv7 activation parameters consistent with pharmacological treatments for certain hyperactivity disorders can restore normal firing rates and spiking correlations. Our results provide key insights into how regulation of a ubiquitous potassium channel class can control the coordination of population spiking activity.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for the Neural Basis of Cognition, Pittsburgh, Pennsylvania.
Gabriel Koch
GK
Ocker
Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania; and Center for the Neural Basis of Cognition, Pittsburgh, Pennsylvania bdoiron@pitt.edu.
Brent
B
Doiron
D000200:Action Potentials; D000818:Animals; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D008959:Models, Neurological; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology
D051656:KCNQ Potassium Channels
model; model neurons; noise correlations; potassium channels; synchrony