Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy

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.

Spike-and-Wave Oscillations Based on the Properties of GABABReceptors

“…This effect is consistent with the experimental finding that the T-current is increased selectively in RE cells in a rat model of absence epilepsy (Tsakiridou et al, 1995).…”

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

“…One extensively studied model is the genetic absence epilepsy rats from Strasbourg (GAERS; Ref. 419), whose T-type currents were larger than those recorded from a seizure-free rat strain (409). Consistent with the enhanced currents, enhanced expression of Ca v 3.2 was detected in the reticular thalamic nuclei, although the changes in current density (50%) were larger than the changes in channel mRNA (20%; Ref.…”

Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat

“…17 Kindling is not the only model of epilepsy where the LVA current is enhanced. In the model of absence epilepsy (GAERS), 44 the enhanced LVA calcium currents in the thalamus can drive rhythmic activities and underlie rebound activity. 8,16,19 Antiepileptic drugs like ethosuximide, trimethadione 9 and valproic acid 23 have been reported to affect LVA calcium currents.…”

“…46 The involvement of the LVA current in kindling epileptogenesis is not unique, because in a model for absence epilepsy (Genetic Absence Epilepsy Rats from Strasbourg or GAERS), the LVA calcium current in thalamic neurons is larger than in a non-epileptic control strain. 44 In the dentate area of the hippocampus, others 32 have described a decrease of the amplitude of the HVA calcium current, mainly attributed to a loss of calcium binding proteins. 24 This implies that although calcium currents are often involved in kindling, their changes are not necessarily the same in different areas of the brain.…”