| Literature DB >> 29268098 |
Mark S Moehle1, Tristano Pancani1, Nellie Byun2, Samantha E Yohn1, George H Wilson2, Johnathan W Dickerson1, Daniel H Remke1, Zixiu Xiang1, Colleen M Niswender3, Jürgen Wess4, Carrie K Jones1, Craig W Lindsley1, Jerri M Rook1, P Jeffrey Conn5.
Abstract
Cholinergic regulation of dopaminergic inputs into the striatum is critical for normal basal ganglia (BG) function. This regulation of BG function is thought to be primarily mediated by acetylcholine released from cholinergic interneurons (ChIs) acting locally in the striatum. We now report a combination of pharmacological, electrophysiological, optogenetic, chemogenetic, and functional magnetic resonance imaging studies suggesting extra-striatal cholinergic projections from the pedunculopontine nucleus to the substantia nigra pars reticulata (SNr) act on muscarinic acetylcholine receptor subtype 4 (M4) to oppose cAMP-dependent dopamine receptor subtype 1 (D1) signaling in presynaptic terminals of direct pathway striatal spiny projections neurons. This induces a tonic inhibition of transmission at direct pathway synapses and D1-mediated activation of motor activity. These studies provide important new insights into the unique role of M4 in regulating BG function and challenge the prevailing hypothesis of the centrality of striatal ChIs in opposing dopamine regulation of BG output.Entities:
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Year: 2017 PMID： 29268098 PMCID： PMC5753765 DOI： 10.1016/j.neuron.2017.12.008
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173