RT Journal Article
SR Electronic
T1 An Ultra-Short Dopamine Pathway Regulates Basal Ganglia Output
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10424
OP 10435
DO 10.1523/JNEUROSCI.4402-08.2009
VO 29
IS 33
A1 Fu-Wen Zhou
A1 Ying Jin
A1 Shannon G. Matta
A1 Ming Xu
A1 Fu-Ming Zhou
YR 2009
UL http://www.jneurosci.org/content/29/33/10424.abstract
AB 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.