Functional contribution of specific brain areas to absence seizures: role of thalamic gap-junctional coupling

• Published in: The European journal of neuroscience 2006-01, Vol.23 (2), p.489-496
• Main Authors: Proulx, Éliane, Leshchenko, Yevgen, Kokarovtseva, Larisa, Khokhotva, Vladislav, El-Beheiry, Mostafa, Snead III, O. Carter, Perez Velazquez, Jose L.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Brain Mapping; Carbenoxolone - pharmacology; Disease Models, Animal; Electrodes; Electroencephalography - methods; epilepsy; Epilepsy, Absence - chemically induced; Epilepsy, Absence - pathology; Epilepsy, Absence - physiopathology; Evoked Potentials - drug effects; Evoked Potentials - physiology; Functional Laterality; gap junctions; Gap Junctions - physiology; in vivo recordings; Methylamines - pharmacology; Rats; Rats, Long-Evans; seizures; Spectrum Analysis - methods; synchrony; thalamus; Thalamus - pathology; Time Factors; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2005.04558.x

The synchronized discharges typical of seizures have a multifactorial origin at molecular, cellular and network levels. During recent years, the functional role of gap‐junctional coupling has received increased attention as a mechanism that may participate in seizure generation. We have investigated the possible functional roles of thalamic and hippocampal gap‐junctional communication (GJC) in the generation of spike‐and‐wave discharges in a rodent model of atypical absence seizures. Seizures in this model spread throughout limbic, thalamic and neocortical areas. Rats were chronically implanted with cannulae to deliver drugs or saline, and local field potentials recordings were performed using intracerebral electrodes positioned in distinct brain areas. Initially, the effects on synaptic transmission of the gap‐junctional blockers used in this study were determined. Neither carbenoxolone (CBX) nor 18‐α‐glycyrrhetinic acid altered chemical synaptic transmission at the concentrations tested. These two compounds, when injected via cannulae into the reticular nucleus of the thalamus (NRT), decreased significantly the duration of seizures as compared with saline injections or injections of the CBX inactive derivative glycyrrhizic acid. CBX injections into the hippocampus resulted in diminished seizure activity as well. NRT injections of trimethylamine, which presumably causes intracellular alkalinization (thereby promoting gap‐junctional opening), enhanced seizures and spindle activity. These observations suggest that, in this rodent model, thalamic and limbic areas are involved in the synchronous paroxysmal activity and that GJC contributes to the spike‐and‐wave discharges.