Simulation of GABA _B -receptor-mediated K⁺ current in thalamocortical relay neurons: tonic firing, bursting, and oscillations

Abstract

Until recently, the presence of γ-aminobutyric acid (GABA) in the thalamus has usually been associated with the ‘classical’ GABA _A Cl⁻-dependent receptor. However, the discovery of a slower, long-lasting, K⁺-dependent inhibitory postsynaptic potential (IPSP) mediated by GABA _B receptors in projection cells of the dorsal lateral geniculate nucleus has led researchers to reconsider its role in modulating the behavior of these cell groups (Crunelli et al. 1988; Crunelli and Leresche 1991). Of particular interest is the role of this K⁺ current in the activation of the low-threshold Ca²⁺ current, I _T , of thalamocortical relay (TCR) neurons responsible for bursting activity (Jahnsen and Llinás 1984a,b). Considering the time scale on which the GABA _B -receptor-activated K⁺ current operates, it is ideally suited to foster sustained rhythmicity in TCR cells reciprocally connected to neurons of the nucleus reticularis thalami (NRT) as well as interneurons at frequencies observed in vivo (Steriade and Llinás 1988). In this study we show that small changes in the duration and amplitude of the K⁺-dependent IPSPs can have marked effects on TCR cell groups including a shift from single-spike firing (tonic) to bursting behavior. We further show that a single GABA _B -mediated IPSP is sufficient to activate the low-threshold Ca²⁺ response and that sustained oscillations are possible given the presence of excitatory TCR connections to GABAergic NRT cells or interneurons of the dorsal lateral thalamus. These combined effects are examined with regard to their role in generating the well known 7 – 14 Hz spindle rhythm as well as slower 6 – 8 Hz oscillations observed in TCR cells in vivo (Steriade and Llinás 1988).