Analysis of the role of the low threshold currents IT and Ih in intrinsic delta oscillations of thalamocortical neurons.

Yimy Amarillo,Germã¡N Mato,Marcela S Nadal

doi:10.3389/fncom.2015.00052

Abstract

Thalamocortical neurons are involved in the generation and maintenance of brain rhythms associated with global functional states. The repetitive burst firing of TC neurons at delta frequencies (1–4 Hz) has been linked to the oscillations recorded during deep sleep and during episodes of absence seizures. To get insight into the biophysical properties that are the basis for intrinsic delta oscillations in these neurons, we performed a bifurcation analysis of a minimal conductance-based thalamocortical neuron model including only the IT channel and the sodium and potassium leak channels. This analysis unveils the dynamics of repetitive burst firing of TC neurons, and describes how the interplay between the amplifying variable mT and the recovering variable hT of the calcium channel IT is sufficient to generate low threshold oscillations in the delta band. We also explored the role of the hyperpolarization activated cationic current Ih in this reduced model and determine that, albeit not required, Ih amplifies and stabilizes the oscillation.

Highlights

Repetitive burst firing of thalamocortical (TC) neurons in the delta band has been linked to the expression of the rhythms that characterize slow wave sleep and the pathological spike and wave discharges of absence epilepsy (McCormick and Bal, 1997; Budde et al, 2005)
An absence epilepsy phenotype is obtained by genetic elimination of HCN2 (Ludwig et al, 2003), which is an Ih channel subunit strongly expressed in TC neurons (Santoro et al, 2000)
Phase Plane and Bifurcation Analysis of a Minimal Model of Thalamocortical Neurons In a previous study, we used a murine TC neuron conductance model to explore the minimal requirements for generating periodic oscillations at delta frequencies (Amarillo et al, 2014)

Summary

Introduction

Repetitive burst firing of thalamocortical (TC) neurons in the delta band has been linked to the expression of the rhythms that characterize slow wave sleep and the pathological spike and wave discharges of absence epilepsy (McCormick and Bal, 1997; Budde et al, 2005). Delta oscillations of thalamocortical neurons abolishes the generation of low threshold spikes (LTS) (Kim et al, 2001), and suppresses the delta oscillations during NREM sleep (Lee et al, 2004). Overexpression of this channel subunit results in a phenotype of pure absence epilepsy in mice (Ernst et al, 2009). An absence epilepsy phenotype is obtained by genetic elimination of HCN2 (Ludwig et al, 2003), which is an Ih channel subunit strongly expressed in TC neurons (Santoro et al, 2000)

Methods

Results

Conclusion