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Quarter Century after the Direct and Indirect Pathways: Towards Comprehensive Understandings of the Basal Ganglia

開催日 2014/9/13
時間 9:00 - 11:00
会場 Room B(501)
Chairperson(s) 南部 篤 / Atsushi Nambu (生理学研究所 生体システム研究部門 / Division of System Neurophysiology, National Institute for Physiological Sciences, Japan)
藤山 文乃 / Fumino Fujiyama (同志社大学・脳科学研究科 / Laboratory of Neural Circuitry, Graduate School of Brain Science, Doshisha University, Kyoto, Japan)

What does dopamine tell striatal neurons through D1 and D2 receptors?

  • S3-B-1-4
  • 知見 聡美 / Satomi Chiken:1 
  • 1:自然科学研究機構 生理学研究所 / Div Syst Neurophysiol, Natl Inst Physiol Sci, and Grad Univ Adv Studies, Okazaki, Japan 

Dopamine (DA) in the basal ganglia (BG) plays a crucial role in controlling voluntary movements. Actually, loss of DA results in severe motor dysfunctions as observed in Parkinson's disease. The striatum, a main input station of the BG, receives excitatory inputs from the cerebral cortex and DAergic inputs from the substantia nigra pars compacta. Striatal projection neurons are divided into two groups: direct pathway neurons with DA D1 receptors (D1Rs) projecting to the internal segment of the globus pallidus (GPi), and indirect pathway neurons with D2 receptors (D2Rs) projecting to the external segment of the globus pallidus (GPe). To clarify the role of DA in information processing through the BG, we recorded neuronal activity in the GPi and GPe under awake state in (1) D1R knockdown (D1RKD) mice whose D1Rs are conditionally and reversibly regulated by doxycycline (Dox), and (2) D2R knockout (D2RKO) mice.
Before Dox administration, both GPi and GPe neurons of D1RKD mice exhibited triphasic responses composed of the early excitation followed by inhibition and late excitation to cortical stimulation, similar to those observed in wild-type mice. However, during suppression of D1R expression by Dox administration, the cortically evoked inhibition in GPi neurons was mostly lost, while no significant changes were observed in GPe neurons. The cortically evoked inhibition is mediated by the cortico-striato-GPi pathway, suggesting that excitability of striato-GPi direct pathway neurons was decreased. In addition, spontaneous motor activities significantly reduced. On the other hand, in D2RKO mice, the cortically evoked inhibition and following excitation in GPe neurons were drastically increased. The cortically evoked inhibition and late excitation are mediated by the cortico-striato-GPe and cotico-striato-GPe-subthalamo-GPe pathways respectively, suggesting that excitability of striato-GPe indirect pathway neurons was increased in D2RKO mice.
These results suggest that DAergic transmission through D1Rs and D2Rs acts as gatekeepers for the information flow through the direct and indirect pathways and appropriate motor actions.

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