Low Threshold Spikes and Rhythmic Oscillations in Thalamic Neurons

Abstract

The electrophysiological activity of thalamic relay neurons is critically dependent upon behavioral state. During drowsiness and quiet sleep (and possibly also during petit mal seizures), the cells may no longer be free to faithfully relay impinging synaptic input to the neocortex. Instead, they are intermittently constrained to fire bursts of action potentials in a synchronized, rhythmic fashion. Underlying these bursts is a slow membrane potential oscillation with a frequency of 7–;14 Hz (but which may be slower during seizures). Whereas the hyper polarizing phase of the cycle is mediated synaptically, possibly by the inhibitory drive of cells in the nucleus reticularis thalami (RE), endogenous properties of the relay neurons themselves are largely responsible for the depolarizing part of the oscillation [6]. Thus, a Ca2+-dependent depolarizing event or “low threshold spike” (LTS) is triggered as the synaptic inhibition decays and the LTS, in turn, evokes a burst of Na+-dependent action potentials that ride upon its peak. Experimental evidence has recently implicated T-type (low threshold) voltage-dependent Ca2+ channels as mediators of the LTS [7]. In what follows we summarize our theoretical work supporting a critical role of the T-type Ca2+ channel in the generation of the LTS. Moreover, we investigate possible mechanisms responsible for the rhythmic firing of RE neurons. Like relay neurons, RE cells also exhibit LTS and bursting behavior [2], although voltage clamp data for these cells are not yet available. We have found that a minimal model of two cells that possess T-type Ca2+ channels and interact with each other via synaptic inhibition is able to generate rhythmic oscillations at an appropriate frequency (about 10 Hz). We show that the oscillatory period can be modulated by both intrinsic cellular properties (kinetics of the T-type Ca2+ channels), and the characteristics of the synaptic inhibition between cells.