Mechanism of an Intrinsic Oscillation in Rat Geniculate Interneurons

Depolarizing current injections produced a rhythmic bursting of action potentials, a bursting oscillation, in a set of local interneurons in the lateral geniculate nucleus (LGN) of rats. The current dynamics underlying this firing pattern have not been determined, though this cell type constitutes an important cellular component of thalamocortical circuitry and contributes to both pathologic and nonpathologic brain states. We thus investigated the source of the bursting oscillation using pharmacological manipulations in LGN slices in vitro and in silico. We found that selective blockade of calcium channel subtypes revealed that high-threshold calcium currents IL and IP contributed strongly to the oscillation. In addition, increased extracellular K+ concentration (decreased K+ currents) eliminated the oscillation. In addition, selective blockade of K+ channel subtypes demonstrated that the calcium-sensitive potassium current (IAHP) was of primary importance. A morphologically simplified, multicompartment model of the thalamic interneuron characterized the oscillation as follows, First, the low-threshold calcium current (IT) provided the strong initial burst characteristic of the oscillation. In addition, alternating fluxes through high-threshold calcium channels and IAHP then provided the continuing oscillation's burst and interburst periods, respectively. This interplay between IL and IAHP contrasts with the current dynamics underlying oscillations in thalamocortical and reticularis neurons, which primarily involve IT and hyperpolarization-activated cation current IH, or IT and IAHP, respectively. These findings thus point to a novel electrophysiological mechanism for generating intrinsic oscillations in a major thalamic cell type. Because local interneurons can sculpt the behavior of thalamocortical circuits, these results suggest new targets for the manipulation of ascending thalamocortical network activity.