Inhibition of GABAergic Transmission as a Model of Hyperactivation of Purkinje Cells in the Rat Cerebellum

• Published in: Biophysics (Oxford) 2020, Vol.65 (1), p.88-94
• Main Authors: Karelina, T. V., Stepanenko, Y. D., Sibarov, D. A., Abushik, P. A., Antonov, S. M.
• Format: Article
• Language: English
• Subjects: Biological and Medical Physics; Biophysics; Calcium channels; Cell Biophysics; Cerebellum; Firing pattern; Glutamic acid receptors; Indoles; N-Methyl-D-aspartic acid receptors; Neurodegeneration; Ontogeny; Physics; Physics and Astronomy; Potassium channels (calcium-gated); Potassium conductance; Purkinje cells; γ-Aminobutyric acid
• ISSN: 0006-3509; 1555-6654
• DOI: 10.1134/S000635092001008X

—Pathological changes in the cerebellum are often associated with dysfunction of Purkinje cells, which is manifested in excessive spike activity. In our experiments, the increase in the frequency of spike activity of Purkinje cells was caused by the suppression of inhibitory transmission by the GABA receptor antagonist gabazin (hydrobromide 6-imino-3-(4-methoxyphenyl)-1(6 H )-pyrazinobutanic acid) contrary to the classical model of neurodegeneration, in which hyperactivation of neurons is caused by the long-term action of high concentrations of excitatory agonists (glutamate or N -methyl-D-aspartate). In adult and young animals, gabazine caused a significant increase in the frequency of Purkinje cell discharges after 25 and 45 min of action, respectively. Thus, this model worked more effectively in adult animals than in young ones, which is due to the ontogenetic features of the formation of the cerebellar cortex. Moreover, the use of NS 309 (6,7-dichloro-1 H -indole-2,3-diketone-3-oxime), a modulator of Ca 2+ -activated K + channels of small conductance, in this model made it possible to compensate for the increase in the frequency of simple spikes induced by the gabazine in the discharge of Purkinje cells to the level of the control values in young and adult rats.