Cholinergic mechanisms in the pathogenesis of genetically-caused absence epilepsy

• Published in: Uspekhi fiziologicheskikh nauk Vol. 34; no. 1; p. 20
• Main Authors: Berdiev, R K, Chepurnov, S A, Chepurnova, N E, van Luijtelaar, E L
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01-01-2003
• Subjects: Animals; Aziridines - toxicity; Brain - physiopathology; Choline - analogs & derivatives; Choline - toxicity; Epilepsy, Absence - genetics; Epilepsy, Absence - physiopathology; Galanin - physiology; Humans; Rats; Receptors, Cholinergic - drug effects; Receptors, Cholinergic - physiology; Thalamus - physiopathology
• ISSN: 0301-1798

Frontoparietal cortex and the thalamocortical circuit comprising reticular thalamic nucleus (RTN) and relay nuclei of the ventrolateral thalamus (VLT) are critical structures in the generation of spike-wave discharges (SWD) during absence seizures. The activity of these nuclei is under the control of the ascending cholinergic projections of nucleus basalis of Meynert. The aim of our study is to make an attempt to change the pattern of SWD in WAG/Rij rats by injecting of cholinotoxine AF64A to the area of RTN. Spontaneous SWD were registered in cortex of WAG/Rij rats with genetically determined absences. The spectral content of SWD was analyzed by means of the Fast Fourier Transformation (FFT) procedure. Unilateral injections of AF64A (1 nmol) to RTN led the decrease in duration and number of SWD comparing to the basal EEG recordings 2 days after the lesion. The FFT analysis showed the disappearance of 17-18 Hz spike on the side of the lesion compared with the intact side. The immunohistochemical study for acetylcholinetransferase (ChaT)-containing neurons showed the loss of ChaT-positive cells in the nucleus basalis area on the side of the lesion. The removal of cholinergic afferentation of RTN and cortex from nucleus basalis inhibits the SWD developing most likely due to the decrease of cortical excitability. Moreover, possibly cholinergic transmission is involved in the transforation of the synchronized phenomena (SWD) to another with close mechanism of generation.