Acetylcholine receptor activation enhances NMDA-mediated responses in the rat neostriatum

The influence of acetylcholine (ACh) upon N-methyl-D-aspartate (NMDA) receptor activation of neostriatal neurons is unknown. In the present study, we used both in vitro intracellular and in vivo electroencephalographic recordings in rats to examine this question. In vitro, iontophoretic application of carbachol, a cholinergic receptor agonist, significantly increased the NMDA-mediated response of neostriatal projection neurons. Carbachol alone had mild excitatory effects. In vivo, intrastriatal NMDA produced focal epileptiform activity restricted to the neostriatum. NMDA applied in conjunction with carbachol produced significantly greater epileptiform activity which propagated to the neocortex. These results suggest that ACh and NMDA receptor co-activation leads to potentiation of the neuronal responses both at the site of the interaction and at the endpoint of the cortico-striato-cortical circuit.