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The Journal of Neuroscience, August 19, 2009, 29(33):10424-10435; doi:10.1523/JNEUROSCI.4402-08.2009

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Cellular/Molecular
An Ultra-Short Dopamine Pathway Regulates Basal Ganglia Output

Fu-Wen Zhou,¹ Ying Jin,¹ Shannon G. Matta,¹ Ming Xu,² and Fu-Ming Zhou¹

¹Department of Pharmacology, University of Tennessee College of Medicine, Memphis, Tennessee 38163, and ²Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois 60637

Correspondence should be addressed to Fu-Ming Zhou, Department of Pharmacology, University of Tennessee College of Medicine, Memphis, TN 38163. Email: fzhou3{at}utmem.edu

Substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus critical for movement control. Its GABA-containing projection neurons intermingle with nigral dopamine (DA) neuron dendrites. Here we show that SNr GABA neurons coexpress dopamine D₁ and D₅ receptor mRNAs and also mRNA for TRPC3 channels. Dopamine induced an inward current in these neurons and increased their firing frequency. These effects were mimicked by D₁-like agonists, blocked by a D₁-like antagonist. D₁-like receptor blockade reduced SNr GABA neuron firing frequency and increased their firing irregularity. These D₁-like effects were absent in D₁ or D₅ receptor knock-out mice and inhibited by intracellularly applied D₁ or D₅ receptor antibody. These D₁-like effects were also inhibited when the tonically active TRPC3 channels were inhibited by intracellularly applied TRPC3 channel antibody. Furthermore, stimulation of DA neurons induced a direct inward current in SNr GABA neurons that was sensitive to D₁-like blockade. Manipulation of DA neuron activity and DA release and inhibition of dopamine reuptake affected SNr GABA neuron activity in a D₁-like receptor-dependent manner. Together, our findings indicate that dendritically released dopamine tonically excites SNr GABA neurons via D₁–D₅ receptor coactivation that enhances constitutively active TRPC3 channels, forming an ultra-short substantia nigra pars compacta SNr dopamine pathway that regulates the firing intensity and pattern of these basal ganglia output neurons.

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Received Sept. 15, 2008; revised July 9, 2009; accepted July 14, 2009.

Correspondence should be addressed to Fu-Ming Zhou, Department of Pharmacology, University of Tennessee College of Medicine, Memphis, TN 38163. Email: fzhou3{at}utmem.edu

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