Cholinergic control of firing pattern and neurotransmission in rat neostriatal projection neurons: Role of Ca_V2.1 and Ca_V2.2 Ca²⁺ channels

Besides a reduction of L-type Ca²⁺-currents (Ca_V1), muscarine and the peptidic M₁-selective agonist, MT-1, reduced currents through Ca_V2.1 (P/Q) and Ca_V2.2 (N) Ca ²⁺ channel types. This modulation was strongly blocked by the peptide MT-7, a specific muscarinic M₁-type receptor antagonist but not significantly reduced by the peptide MT-3, a specific muscarinic M ₄-type receptor antagonist. Accordingly, MT-7, but not MT-3, blocked a muscarinic reduction of the afterhyperpolarizing potential (AHP) and decreased the GABAergic inhibitory postsynaptic currents (IPSCs) produced by axon collaterals that interconnect spiny neurons. Both these functions are known to be dependent on P/Q and N types Ca²⁺ channels. The action on the AHP had an important effect in increasing firing frequency. The action on the IPSCs was shown to be caused presynaptically as it coursed with an increase in the paired-pulse ratio. These results show: first, that muscarinic M ₁-type receptor activation is the main cholinergic mechanism that modulates Ca²⁺ entry through voltage-dependent Ca²⁺ channels in spiny neurons. Second, this muscarinic modulation produces a postsynaptic facilitation of discharge together with a presynaptic inhibition of the GABAergic control mediated by axon collaterals. Together, both effects would tend to recruit more spiny neurons for the same task.