Oxotremorine suppresses thalamocortical oscillations via thalamic muscarinic acetylcholine receptors

We investigated whether the local intrathalamic infusion of a muscarinic ac etylcholine receptor agonist (oxotremorine) at either the reticular nucleus of thalamus (NRT) or the ventroposteromedial nucleus of thalamus (VPM) sup presses thalamocortically generated neocortical high-voltage spindles (HVSs ). In addition, we studied whether the intracerebroventricular (ICV) infusi on of a selective muscarinic M-2 acetylcholine receptor antagonist (methoct ramine) could block the suppression of HVSs induced by either systemic (IP) administration of an anticholinesterase drug [tetrahydroamiaoacridine (THA )] or ICV infusion of oxotremorine in rats. Intrathalamic administration of oxotremorine at 3 and 15 mu g in the NRT, and at 15 mu g in the VPM suppre ssed HVSs. ICV oxotremorine at 30 and 100 mu g and IP THA at 3 mg/kg decrea sed HVSs. ICV methoctramine at 100 mu g increased HVSs and completely block ed the decrease in HVSs produced by oxotremorine 100 mu g and THA 3 mg/kg. The results suggest that activation of muscarinic M-2 acetylcholine recepto rs in thalamic nuclei (NRT and VPM) can suppress thalamocortical oscillatio ns and that ICV or systemically administered drugs that activate either dir ectly (oxotremorine and methoctramine) or indirectly (THA) the muscarinic M -2 acetylcholine receptors may modulate neocortical HVSs via the thalamus.