Conditional ablation of striatal neuronal types containing dopamine D2 receptor disturbs coordination of basal ganglia function

Hiromi Sano, Yasunobu Yasoshima, Natsuki Matsushita, Takeshi Kaneko, Kenji Kohno, Ira Pastan, Kazuto Kobayashi

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

Dopamine (DA) exerts synaptic organization of basal ganglia circuitry through a variety of neuronal populations in the striatum. We performed conditional ablation of striatal neuronal types containing DA D2 receptor (D2R) by using immunotoxin-mediated cell targeting. Mutant mice were generated that express the human interleukin-2 receptor α-subunit under the control of the D2R gene. Intrastriatal immunotoxin treatment of the mutants eliminated the majority of the striatopallidal medium spiny neurons and cholinergic interneurons. The elimination of these neurons caused hyperactivity of spontaneous movement and reduced motor activation in response to DA stimulation. The elimination also induced upregulation of GAD gene expression in the globus pallidus (GP) and downregulation of cytochrome oxidase activity in the subthalamic nucleus (STN), whereas it attenuated DA-induced expression of the immediate-early genes (IEGs) in the striatonigral neurons. In addition, chemical lesion of cholinergic interneurons did not alter spontaneous movement but caused a moderate enhancement in DA-induced motor activation. This enhancement of the behavior was accompanied by an increase in the IEG expression in the striatonigral neurons. These data suggest that ablation of the striatopallidal neurons causes spontaneous hyperactivity through modulation of the GP and STN activity and that the ablation leads to the reduction in DA-induced behavior at least partly through attenuation of the striatonigral activity as opposed to the influence of cholinergic cell lesion. We propose a possible model in which the striatopallidal neurons dually regulate motor behavior dependent on the state of DA transmission through coordination of the basal ganglia circuitry.

Original languageEnglish
Pages (from-to)9078-9088
Number of pages11
JournalJournal of Neuroscience
Volume23
Issue number27
DOIs
Publication statusPublished - 08-10-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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