Mechanism of an Intrinsic Oscillation in Rat Geniculate Interneurons

Author:

Griffith Erica Y.ORCID,ElSayed MohamedORCID,Dura-Bernal SalvadorORCID,Neymotin Samuel A.ORCID,Uhlrich Daniel J.,Lytton William W.ORCID,Zhu J. Julius

Abstract

AbstractDepolarizing 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 non-pathologic brain states. We thus investigated the source of the bursting oscillation using pharmacological manipulations in LGN slicesin vitroandin silico.1. Selective blockade of calcium channel subtypes revealed that high-threshold calcium currents ILand IPcontributed strongly to the oscillation.2. Increased extracellular K+concentration (decreased K+currents) eliminated the oscillation.3. 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:1. The low-threshold calcium current (IT) provided the strong initial burst characteristic of the oscillation.2. Alternating fluxes through high-threshold calcium channels andIAHPthen provided the continuing oscillation’s burst and interburst periods respectively. This interplay between ILand IAHPcontrasts with the current dynamics underlying oscillations in thalamocortical and reticularis neurons, which primarily involve ITand IH, or ITand IAHPrespectively. 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.

Publisher

Cold Spring Harbor Laboratory

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