An ultra-short dopamine pathway regulates basal ganglia output

Fuwen Zhou, Ying Jin, Shannon G. Matta, Ming Xu, Fuming Zhou

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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. D 1-like receptor blockade reduced SNrGABA 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 3 SNr dopamine pathway that regulates the firing intensity and pattern of these basal ganglia output neurons.

Original languageEnglish (US)
Pages (from-to)10424-10435
Number of pages12
JournalJournal of Neuroscience
Volume29
Issue number33
DOIs
StatePublished - Aug 19 2009

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Basal Ganglia
GABAergic Neurons
Dopamine
Dopaminergic Neurons
Neurons
Dopamine D5 Receptors
Dopamine D1 Receptors
Messenger RNA
Antibodies
Substantia Nigra
Dendrites
Knockout Mice
gamma-Aminobutyric Acid
Pars Reticulata
TRPC3 cation channel

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

An ultra-short dopamine pathway regulates basal ganglia output. / Zhou, Fuwen; Jin, Ying; Matta, Shannon G.; Xu, Ming; Zhou, Fuming.

In: Journal of Neuroscience, Vol. 29, No. 33, 19.08.2009, p. 10424-10435.

Research output: Contribution to journalArticle

Zhou, Fuwen ; Jin, Ying ; Matta, Shannon G. ; Xu, Ming ; Zhou, Fuming. / An ultra-short dopamine pathway regulates basal ganglia output. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 33. pp. 10424-10435.
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