Oxotremorine suppresses thalamocortical oscillations via thalamic muscarinic acetylcholine receptors

Abstract

We investigated whether the local intrathalamic infusion of a muscarinic acetylcholine receptor agonist (oxotremorine) at either the reticular nucleus of thalamus (NRT) or the ventroposteromedial nucleus of thalamus (VPM) suppresses thalamocortically generated neocortical high-voltage spindles (HVSs). In addition, we studied whether the intracerebroventricular (ICV) infusion of a selective muscarinic M₂ acetylcholine receptor antagonist (methoctramine) could block the suppression of HVSs induced by either systemic (IP) administration of an anticholinesterase drug [tetrahydroaminoacridine (THA)] or ICV infusion of oxotremorine in rats. Intrathalamic administration of oxotremorine at 3 and 15 μg in the NRT, and at 15 μg in the VPM suppressed HVSs. ICV oxotremorine at 30 and 100 μg and IP THA at 3 mg/kg decreased HVSs. ICV methoctramine at 100 μg increased HVSs and completely blocked the decrease in HVSs produced by oxotremorine 100 μg and THA 3 mg/kg. The results suggest that activation of muscarinic M₂ acetylcholine receptors in thalamic nuclei (NRT and VPM) can suppress thalamocortical oscillations and that ICV or systemically administered drugs that activate either directly (oxotremorine and methoctramine) or indirectly (THA) the muscarinic M₂ acetylcholine receptors may modulate neocortical HVSs via the thalamus.