線条体におけるアセチルコリンとドーパミンの生理的相互作用

Physiological Interaction between Acetylcholine and Dopamine in the Striatum

はじめに

　ドーパミンの枯渇するパーキンソン病で，最初に確立した治療法が抗コリン剤の投与であったことからわかるように，アセチルコリンとドーパミンは互いに拮抗し，ときには共同して作用する。脳の中で両者が最も密接に会合する場は線条体（背側線条体と腹側線条体もしくは側坐核）である。線条体は，Dahlstrom & Fuxe（1964）の分類によるA8，A9，A10のドーパミンニューロンから極めて濃密な投射を受けていて，ドーパミン受容体の分布もまた極めて高濃度である。アセチルコリンの場合は，線条体と嗅結節に限っては他のほとんどの脳部位と異なり内在する自前のcholinergic interneuronからアセチルコリンを供給される。

　本稿では線条体のcholinergic interneuronがドーパミンとどのように関わって行動発現に寄与するのか，これまで明らかになってきた線条体局所回路の性質から，考察してみたい。

Abstract

　The breakdown of the balance between acetylcholine and dopamine in the striatum is known to cause a variety of neurological diseases.　Physiologically,the association between sensory cues and reward during behavioral learning gradually forms a conditional pause response in the firing of the tonically active cholinergic interneurons in the striatum.　Simultaneous recordings of striatal cholinergic interneurons and midbrain dopaminergic neurons during the task revealed that the pause response was well synchronized with the increase in the firing frequency of the dopaminergic neurons.　Recent studies have indicated that the content of released dopamine is proportional to the firing frequency of the dopaminergic neurons unless the nicotinic receptors are activated,but it remains unaltered if the receptors are bound by acetylcholine.　Therefore,dopamine release would be dramatically increased during the pause response of the cholinergic neurons.　The pause response is composed of an initial depolarization phase,a pause phase,and a rebound facilitation phase.　Dopamine D5 receptor-dependent long-term potentiation underlies the initial depolarization phase,which causes the ensuing pause phase.　The termination of the pause is further delayed by suppression of Ih and sodium channels through dopamine D2 receptor activation.　This facilitates the synaptic efficacy of the striatal medium spiny projection neurons,which enables the execution of action commands with an improved signal-to-noise ratio.