Inward rectifier potassium current I Kir promotes the intrinsic pacemaker activity of thalamocortical neurons

Abstract

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (< 4 Hz), which are the frequencies of the physiological oscillations during N-REMsleep, or pathological ones during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that up-regulation of the small and overlooked inward rectifier potassium current IKir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mice TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explainshow the unique properties of IKir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage and time-dependent interaction of IKir andIh that bestows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. The bifurcation analysis of conductance based models of increasing complexity demonstrates that IKir induces bistability of the membrane potential at the same time that induces sustained oscillations in combination with Ih and increases the robustness of IT mediated oscillations.