Muscarinic receptors involved in the subthreshold cholinergic actions of neostriatal spiny neurons

Administration of the peptide MT‐1 (48 nM), a selective agonist of muscarinic M 1 ‐type receptors, mimicked the subthreshold actions of muscarine (1 μM) on neostriatal neurons, i.e., it produced a reduction in subthreshold inward rectification leading to an enhancement in input resistance (R N ) and evoked discharge. In all recorded cells, MT‐1 effects remained in the presence of the specific peptidergic antagonist of the M 4 ‐type receptor, MT‐3 (10 nM), but were blocked by the specific M 1 ‐type receptor antagonist MT‐7 (5 nM). These results suggest that most muscarinic facilitatory actions in the subthreshold voltage range occur through M 1 ‐type receptors. However, in a fraction of cells (40%) muscarine produced an excitability enhancement not blocked by MT‐7. This additional facilitatory action, not present when using MT‐1, was blocked by MT‐3, suggesting it was mediated by M 4 ‐type receptor activation. This facilitation could not be blocked by Cs + , TTX, or Cd 2+ , but only by a reduction in extracellular sodium. This result is the first evidence that M 4 ‐type receptor activation enhances a cationic inward current in a fraction of neostriatal projection neurons. Synapse 46:215–223, 2002. © 2002 Wiley‐Liss, Inc.