The role of cholinergic interneurons in regulating corticostriatal culture response to dopaminergic stimulation

Abstract

Introduction: We investigated the cholinergic regulation of striatal response to dopaminergic stimulation. Methods: Rat neurons for dissociated striatal cultures were harvested from E18.5. E14.5 neurons were supplemented to the cultures to provide cholinergic interneurons. Cultures were stimulated with dopamine D1R or D2R agonist and antagonist and changes in c-FOS and EGR-1 expression and DARPP-32 phosphorylation were assessed by Western blots. Electrophysiological recordings were performed using multielectrode array. Results: Molecular studies: Although no significant changes were observed, trends showed that cholinergic innervation produced a differential regulation of c-FOS and EGR-1 expression associated with D1R and D2R signaling. Electrophysiological analysis: Significantly more activity was detected in cultures without cholinergic interneurons. Moreover, an increase in firing was seen in cultures with cholinergic interneurons following the addition of a muscarinic 1 receptor antagonist. Conclusion: Our results suggest a differential impact of cholinergic regulation on D1R and D2R signaling pathways.