H-Channels Affect Frequency, Power and Amplitude Fluctuations of Neuronal Network Oscillations

Abstract

Oscillations in network activity are ubiquitous in the brain and are involved in diverse cognitive functions. Oscillation characteristics, such as power, frequency, and temporal structure, depend on both network connectivity and intrinsic cellular properties, such as ion channel composition. An important class of channels, with key roles in regulating cell excitability, are h-channels. The h-current (Ih) is a slow, hyperpolarization-activated, depolarizing current that contributes to neuronal resonance and membrane potential. The impact of Ih on network oscillations, however, remains poorly understood. To elucidate the network effects of Ih, we used a computational model of a generic oscillatory neuronal network consisting of inhibitory and excitatory cells that were externally driven by excitatory action potentials and sustained depolarizing currents. We found that Ih increased the oscillation frequency and, in combination with external action potentials, representing input from areas outside the network, strongly decreased the synchrony of firing. As a consequence, the oscillation power and the duration of episodes during which the network exhibited high-amplitude oscillations were greatly reduced in the presence of Ih. Our results suggest that modulation of Ih or impaired expression of h-channels, as observed in epilepsy, could, by affecting oscillation dynamics, markedly alter network-level activity and potentially influence oscillation-dependent cognitive processes such as learning, memory and attention.

Dynamical Mechanism of Hyperpolarization-Activated Non-specific Cation Current Induced Resonance and Spike-Timing Precision in a Neuronal Model

“…The marked characteristics of the electrophysiological activities induced by I h are the voltage sag and post-inhibitory rebound (spike) to hyperpolarization stimulus, due to I h is a slow inward current activated by the hyperpolarization stimulation rather than depolarization stimulation (Ascoli et al, 2010 ; Engbers et al, 2011 ; Gastrein et al, 2011 ; Pavlov et al, 2011 ; Gonzalez et al, 2015 ). Furthermore, the experimental studies found that I h can induce subthreshold membrane resonance and enhance spike-timing precision characterized by the standard deviation ( STD ) or coefficient variation ( CV ) of the interspike intervals (ISIs) (Zemankovics et al, 2010 ; Gastrein et al, 2011 ; Pavlov et al, 2011 ; Borel et al, 2013 ; Gonzalez et al, 2015 ).…”

“…The marked characteristics of the electrophysiological activities induced by I h are the voltage sag and post-inhibitory rebound (spike) to hyperpolarization stimulus, due to I h is a slow inward current activated by the hyperpolarization stimulation rather than depolarization stimulation (Ascoli et al, 2010 ; Engbers et al, 2011 ; Gastrein et al, 2011 ; Pavlov et al, 2011 ; Gonzalez et al, 2015 ). Furthermore, the experimental studies found that I h can induce subthreshold membrane resonance and enhance spike-timing precision characterized by the standard deviation ( STD ) or coefficient variation ( CV ) of the interspike intervals (ISIs) (Zemankovics et al, 2010 ; Gastrein et al, 2011 ; Pavlov et al, 2011 ; Borel et al, 2013 ; Gonzalez et al, 2015 ). Resonance means that impedance profile of a neuron to external stimulus reaches a maximal value at a certain value corresponding to an intrinsic frequency preference (Rotstein, 2015 ; Vazifehkhah et al, 2015 ), which is an important factor related to the rhythmic oscillations (Gasparini and DiFrancesco, 1997 ; Hutcheon and Yarom, 2000 ; Giocomo et al, 2007 ; Moca et al, 2014 ; Gonzalez et al, 2015 ).…”

“…Furthermore, the experimental studies found that I h can induce subthreshold membrane resonance and enhance spike-timing precision characterized by the standard deviation ( STD ) or coefficient variation ( CV ) of the interspike intervals (ISIs) (Zemankovics et al, 2010 ; Gastrein et al, 2011 ; Pavlov et al, 2011 ; Borel et al, 2013 ; Gonzalez et al, 2015 ). Resonance means that impedance profile of a neuron to external stimulus reaches a maximal value at a certain value corresponding to an intrinsic frequency preference (Rotstein, 2015 ; Vazifehkhah et al, 2015 ), which is an important factor related to the rhythmic oscillations (Gasparini and DiFrancesco, 1997 ; Hutcheon and Yarom, 2000 ; Giocomo et al, 2007 ; Moca et al, 2014 ; Gonzalez et al, 2015 ). For example, hippocampal pyramidal neurons (Hu et al, 2002 ; Zemankovics et al, 2010 ; Gastrein et al, 2011 ; Borel et al, 2013 ) exhibit subthreshold resonance to the injection of sinusoidal current, and their resonant properties contribute to the emergence of Theta oscillations (Zemankovics et al, 2010 ; Stark et al, 2013 ).…”

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

“…Reversal potentials and decay rates (table 1) were obtained from existing models 39,41 and from the literature (GABAB 42 , M-channel 43,44 , H-channel 45 ). M-channels are responsible for m-currents; noninactivating voltage-gated potassium currents, which may be important to the intrinsic dynamics (oscillations) of the cell membrane 44 .…”

“…M-channels are responsible for m-currents; noninactivating voltage-gated potassium currents, which may be important to the intrinsic dynamics (oscillations) of the cell membrane 44 . H-channels produce hyperpolarisation activated currents, which not only have a role in the regulation of the resting membrane potential 46 but may contribute to macroscopic network oscillations 45 . The G-protein coupled GABAB receptor has also been linked to macroscale oscillations, including in the gamma range 47 , possibly through its ability to re-balance the excitation-inhibition balance through interactions with NMDA receptor mediated currents 48 .…”