Supersensitive presynaptic dopamine D2 receptor inhibition of the striatopallidal projection in nigrostriatal dopamine-deficient mice

Wei Wei, Li Li, Guoliang Yu, Shengyuan Ding, Chengyao Li, Fuming Zhou

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The dopamine (DA) D2 receptor (D2R)-expressing medium spiny neurons (D2-MSNs) in the striatum project to and inhibit the GABAergic neurons in the globus pallidus (GP), forming an important link in the indirect pathway of the basal ganglia movement control circuit. These striato-pallidal axon terminals express presynaptic D2Rs that inhibit GABA release and thus regulate basal ganglion function. Here we show that in transcription factor Pitx3 gene mutant mice with a severe DA loss in the dorsal striatum mimicking the DA denervation in Parkinson's disease (PD), the striatopallidal GABAergic synaptic transmission displayed a heightened sensitivity to presynaptic D2R-mediated inhibition with the dose-response curve shifted to the left, although the maximal inhibition was not changed. Functionally, low concentrations of DA were able to more efficaciously reduce the striatopallidal inhibition-induced pauses of GP neuron activity in DA-deficient Pitx3 mutant mice than in wild-type mice. These results demonstrate that presynaptic D2R inhibition of the striatopallidal synapse becomes supersensitized after DA loss. These supersensitive D2Rs may compensate for the lost DA in PD and also induce a strong disinhibition of GP neuron activity that may contribute to the motor-stimulating effects of dopaminergic treatments in PD.

Original languageEnglish (US)
Pages (from-to)2203-2216
Number of pages14
JournalJournal of Neurophysiology
Volume110
Issue number9
DOIs
StatePublished - Nov 1 2013

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Dopamine D2 Receptors
Dopamine
Globus Pallidus
Presynaptic Receptors
Parkinson Disease
Basal Ganglia
Neurons
GABAergic Neurons
Presynaptic Terminals
Denervation
Synaptic Transmission
Synapses
gamma-Aminobutyric Acid
Transcription Factors
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Supersensitive presynaptic dopamine D2 receptor inhibition of the striatopallidal projection in nigrostriatal dopamine-deficient mice. / Wei, Wei; Li, Li; Yu, Guoliang; Ding, Shengyuan; Li, Chengyao; Zhou, Fuming.

In: Journal of Neurophysiology, Vol. 110, No. 9, 01.11.2013, p. 2203-2216.

Research output: Contribution to journalArticle

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