Cholinergic Control of Firing Pattern and Neurotransmission in Rat Neostriatal Projection Neurons: Role of Ca_V2.1 and Ca_V2.2 Ca²⁺Channels

Abstract

Besides a reduction of L-type Ca2+-currents (Ca(V)1), muscarine and the peptidic M1-selective agonist, MT-1, reduced currents through Ca(V)2.1 (P/Q) and Ca(V)2.2 (N) Ca2+ 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 M4-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 M1-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.

Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses

“…1E) of the ''unitary'' IPSCs recorded from SPN3SPN connections (Fig. 1F) was found (32,(40)(41)(42). First, shape index plots (graphing half widths vs. rise times) of mean IPSCs (GP3NSt, empty circles; SPN3SPN, filled circles) showed no significant differences between these two connections ( Fig.…”

“…IPSCs between SPNs were also recorded after antidromic stimulation of striofugal axons at the globus pallidus (GP) (called the GP3NSt connection to avoid confusion) ( Fig. 1 A) (32,(40)(41)(42) in the presence of glutamate receptor blockers (10 M CNQX plus 50 M APV). These responses were sensitive to 10 M bicuculline (Fig.…”

Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons

“…Activation of A 1 -receptors mainly reduce Ca V 2.2 channels current [40,41]. Once Ca v 2.2 current was blocked, low adenosine concentrations (100 nM) could no longer reduce Ca 2+ -current further in any cell tested, suggesting that main current component targeted by A 1 -receptors is Ca V 2.2.…”

“…Solution changes used a microvalve system (Lee; Essex, CT, USA) allowing reversibly applications [41]. Substances used were: ω-conotoxin GVIA (ω-CgTx-GVIA), ω-agatoxin TK (ω-AgTx), tetrodotoxin (TTX) (from Alomone Labs; Jerusalem, Israel); nicardipine, adenosine (Sigma-Aldrich-RBI, St. Louis, MO).…”

“…A main reason is, precisely, the relation of these channels with neuronal excitability and transmitter release [5,21,23,33,40,41,46,48,67]. SPNs express several classes of Ca V 1 and Ca V 2 channels [5,6,8,9,38,40,42,48].…”