RRC ID 62684
Author Suzuki E, Momiyama T.
Title M1 muscarinic acetylcholine receptor-mediated inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons.
Journal Eur J Neurosci
Abstract Acetylcholine (ACh) modulates neurotransmitter release in the central nervous system. Although GABAergic transmission onto the striatal cholinergic interneurons (ChIN) is modulated by dopamine receptors, cholinergic modulation of the same synapse is still unknown. In the present study, modulatory roles of ACh in the GABAergic transmission from striatal medium spiny neurons (MSNs) onto ChIN were investigated using optogenetics and whole-cell patch-clamp technique in juvenile and young-adult mice brain slices. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal electrical- or blue-light stimulation. Bath application of carbachol, a muscarinic ACh receptor agonist, suppressed the amplitude of IPSCs in a concentration-dependent manner in both age groups. A choline esterase inhibitor, physostigmine, also suppressed the amplitude of IPSCs. In the presence of a membrane permeable M1 muscarine receptor antagonist, pirenzepine, carbachol-induced suppression of IPSCs was antagonized, whereas a M2 muscarine receptor antagonist, a M4 receptor antagonist, or a membrane impermeable M1 receptor antagonist did not antagonize carbachol-induced suppression of IPSCs. Retrograde cannabinoid cascade via cannabinoid receptor 1 was not involved in carbachol-induced inhibition. Furthermore, carbachol did not affect amplitude of inward currents induced by puff application of GABA, whereas coefficient of variation of IPSCs was significantly increased by carbachol. These results suggest that activation of presynaptic M1 muscarine receptors located on the GABAergic terminals including intracellular organelle of MSNs inhibits GABA release onto ChIN.
Volume 53(3)
Pages 796-813
Published 2021-2-1
DOI 10.1111/ejn.15074
PMID 33270289
MeSH Acetylcholine* Animals Cholinergic Agents Interneurons Mice Neurons Receptor, Muscarinic M1* Synaptic Transmission gamma-Aminobutyric Acid
IF 3.115
Mice RBRC02317 RBRC05843