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Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M4 Muscarinic Receptor.
Moehle, Mark S; Pancani, Tristano; Byun, Nellie; Yohn, Samantha E; Wilson, George H; Dickerson, Johnathan W; Remke, Daniel H; Xiang, Zixiu; Niswender, Colleen M; Wess, Jürgen; Jones, Carrie K; Lindsley, Craig W; Rook, Jerri M; Conn, P Jeffrey.
Afiliación
  • Moehle MS; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Pancani T; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Byun N; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
  • Yohn SE; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Wilson GH; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
  • Dickerson JW; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Remke DH; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Xiang Z; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Niswender CM; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Wess J; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD, USA.
  • Jones CK; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Lindsley CW; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Rook JM; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
  • Conn PJ; Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: jeff.conn@vanderbilt.edu.
Neuron ; 96(6): 1358-1372.e4, 2017 12 20.
Article en En | MEDLINE | ID: mdl-29268098
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ganglios Basales / Dopamina / Receptor Muscarínico M4 / Neuronas Colinérgicas / Porción Reticular de la Sustancia Negra Límite: Animals Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ganglios Basales / Dopamina / Receptor Muscarínico M4 / Neuronas Colinérgicas / Porción Reticular de la Sustancia Negra Límite: Animals Idioma: En Año: 2017 Tipo del documento: Article