Excitatory synaptic transmissions to MSNs are both directly and indirectly regulated by muscarinic receptor signaling. First, glutamatergic EPSCs are presynaptically suppressed by cholinergic agonists [41] through direct activation of mAChRs on presynaptic terminals [42]. Second, postsynaptic activation of M1 receptor can enhance responsiveness of MSNs when they do receive excitatory input. It is hypothesized that the cholinergic system highlights activated excitatory inputs but suppresses background excitation to improve the signal-to-noise ratio of information carried by glutamatergic synapses in the striatum [43].
