Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function.
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.
Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
S
S
Kaneko
T
T
Hikida
D
D
Watanabe
H
H
Ichinose
T
T
Nagatsu
R J
RJ
Kreitman
I
I
Pastan
S
S
Nakanishi
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001479:Basal Ganglia / Q000166:cytology / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D015536:Down-Regulation; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D000922:Immunotoxins; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D016627:Oxidopamine / Q000494:pharmacology; D011187:Posture; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D013373:Substance P / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D018491:Dopamine Agonists; D004745:Enkephalins; D000922:Immunotoxins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate; D013373:Substance P; D016627:Oxidopamine; D002795:Choline O-Acetyltransferase; D001058:Apomorphine; D000109:Acetylcholine; D004298:Dopamine