Abstract
The properties of voltage-dependent calcium currents were compared in thalamic neurons acutely dissociated from a rat model of absence epilepsy, designated as Genetic Absence Epilepsy Rat from Strasbourg (GAERS), and from a Nonepileptic Control strain (NEC). Two populations of neurons were isolated: thalamocortical relay neurons of the nucleus ventrobasalis (VB) and neurons of the nucleus reticularis (RT) of the thalamus. Whole-cell patch-clamp analysis demonstrated an increase in the amplitude of the calcium (Ca2+) current with a low threshold of activation (IT) in RT neurons of GAERS in comparison to that of the seizure-free rat strain (-198 +/- 19 pA and -128 +/- 14 pA, respectively), whereas the sustained component (IL) was not significantly different. The kinetic properties, voltage dependence, and basic pharmacological sensitivity of the Ca2+ conductances were similar in the two populations of neurons. The amplitude of both IT and IL in RT neurons increased after birth, and differences in IT between GAERS and NEC attained significance after postnatal day 11. At corresponding ages, the Ca2+ currents in VB thalamocortical relay neurons were not altered in GAERS in comparison to those in NEC. We conclude that the selective increase in IT of RT neurons enhances the probability of recurrent intrathalamic burst activity, thereby strengthening the synchronizing mechanisms in thalamocortical systems, and, as such, represents a possible primary neuronal dysfunction that relates to the pathological increase in synchronization underlying the generation of bilateral and synchronous spike and wave discharges (SWDs) in an established genetic model of generalized epilepsy.