Synaptic Integration Mediated by Striatal Cholinergic Interneurons in Basal Ganglia Function

Author:

Kaneko Satoshi1,Hikida Takatoshi1,Watanabe Dai1,Ichinose Hiroshi2,Nagatsu Toshiharu2,Kreitman Robert J.3,Pastan Ira3,Nakanishi Shigetada1

Affiliation:

1. Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.

2. Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan.

3. Laboratory of Molecular Biology, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

The physiological role of striatal cholinergic interneurons was investigated with immunotoxin-mediated cell targeting (IMCT). Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual recovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactive state by stimulation and suppression of striatonigral and striatopallidal neurons, respectively. D1 and D2 dopamine receptors were then down-regulated, relieving dopamine-predominant synaptic perturbation but leaving a defect in controlling dopamine responses. The acetylcholine-dopamine interaction is concertedly and adaptively regulated for basal ganglia synaptic integration.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference40 articles.

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