Effects of I_hand TASK-like shunting current on dendritic impedance in layer 5 pyramidal-tract neurons

Abstract

Pyramidal neurons in neocortex have complex input-output relationships that depend on their morphologies, ion channel distributions, and the nature of their inputs, but which cannot be replicated by simple integrate-and-fire models. The impedance properties of their dendritic arbors, such as resonance and phase shift, shape neuronal responses to synaptic inputs and provide intraneuronal functional maps reflecting their intrinsic dynamics and excitability. Experimental studies of dendritic impedance have shown that neocortical pyramidal tract neurons exhibit distance-dependent changes in resonance and impedance phase with respect to the soma. We therefore investigated how well several biophysically-detailed multi-compartment models of neocortical layer 5 pyramidal tract neurons reproduce the location-dependent impedance profiles observed experimentally. Each model tested here exhibited location-dependent impedance profiles, but most captured either the observed impedance amplitude or phase, not both. The only model that captured features from both incorporates HCN channels and a shunting current, like that produced by Twik-related acid-sensitive K+(TASK) channels. TASK-like channel activity in this model was dependent on local peak HCN channel conductance (Ih). We found that while this shunting current alone is insufficient to produce resonance or realistic phase response, it modulates all features of dendritic impedance, including resonance frequencies, resonance strength, synchronous frequencies, and total inductive phase. We also explored how the interaction of Ih and a TASK-like shunting current shape synaptic potentials and produce degeneracy in dendritic impedance profiles, wherein different combinations of Ih and shunting current can produce the same impedance profile.New & NoteworthyWe simulated chirp current stimulation in the apical dendrites of 5 biophysically-detailed multi-compartment models of neocortical pyramidal tract neurons and found that a combination of HCN channels and TASK-like channels produced the best fit to experimental measurements of dendritic impedance. We then explored how HCN and TASK-like channels can shape the dendritic impedance as well as the voltage response to synaptic currents.

Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells

“…In line with this, in [Magee, 1999], pharmacological blockage of I h increased the amplitude of distally elicited EPSPs compared to proximally elicited ones in a CA1 neuron. Computational models have suggested that the observed phenomena could be caused by secondary mechanisms, where a blockage or altered expression of I h channels also indirectly affects conductance of other ion channels, such as Twik-related acid-sensitive K + (TASK) channels [Migliore and Migliore, 2012, Kelley et al, 2021]. Here, focusing solely on L5PCs, we explored by means of computational modelling the possibility that the inhibitory actions attributed to I h activity are caused by direct shunting effects of the current without concurrent changes in the conductance of other ion channels.…”

“…Instead, they suggested that I h current is always coupled to another ionic current (i.e., when I h is blocked, the other current is blocked too) that drives the shunt-inhibition effects observed in experiments. [Kelley et al, 2021] examined a range of neocortical L5PC models, and suggested that a coupling of TASK-like channel with the I h currents as delineated in [Migliore and Migliore, 2012] provided the best fit to experimental impedance amplitude and phase data. While it is possible that different mechanisms modulate I h influence on neuron excitability on different regions, our models suggest that when using a realistically morphological model of an L5PC, T-type Ca 2+ channels and not M-type K + channels have a role in the shunting or excitatory effects of I h currents.…”

“…Instead, they suggested that I h current is always coupled to another ionic current (i.e., when I h is blocked, the other current is blocked too) that drives the shunt-inhibition effects observed in experiments. [Kelley et al, 2021] examined a range of neocortical L5PC models, and suggested that a coupling of TASK-like channel with the I h currents as delineated in [Migliore and Migliore, 2012] provided the best fit to experimental impedance amplitude and phase data.…”