Short term depression of gap junctional coupling in reticular thalamic neurons of absence epileptic rats

Abstract

Introduction Neurons in the reticular-thalamic-nucleus (RTN) are coupled by electrical synapses, which play a major role in regulating synchronous activity. This study investigates electrical coupling in RTN neurons from a rat model of childhood-absence epilepsy, Genetic-Absence-Epilepsy-Rats from Strasbourg (GAERS), compared with a Non-Epileptic-Control strain (NEC), in order to assess the impact on pathophysiological rhythmogenesis. Methods Whole-cell recordings were obtained from pairs of RTN neurons of GAERS and NEC in vitro. Coupling was determined by injection of hyperpolarizing current-steps in one cell and monitoring evoked voltage responses in both activated and coupled cell. The coupling coefficient (cc) was compared under resting condition, during pharmacological interventions and repeated activation using series of current injections. Effect of gap-junctional coupling on seizure expression was investigated by application of gap-junctional blockers into RTN of GAERS in vivo. Results CC at resting conditions did not differ between GAERS and NEC. During repeated activation, cc declined in GAERS but not in NEC. This depression in cc restored within 25 s and was prevented by intracellular presence of BAPTA in the activated but not in the coupled cell. Local application of gap-junction blockers into RTN of GAERS in vivo resulted in a decrease of SWD activity. Discussion Repeated activation results in a short-term-depression (STD) of gap-junctional coupling in RTN neurons of GAERS, depending on intracellular Ca²⁺ mechanisms in the activated cell. Since blockage of gap-junctions in vivo results in a decrease of SWD activity, the STD observed in GAERS is considered a compensatory mechanism, aimed to dampen SWD activity.

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