前頭前野におけるドーパミン機能障害の計算論的研究

抄録

Dopamine dysfunction is generally recognized as a trigger that produces loss of motor control and various cognitive dysfunctions. In particular, the importance of dopamine D1 receptors in regulating working memory has been emphasized ever since experimental studies found that working memory performance demonstrates an inverted U-shape property according to dopamine D1 receptor activation in the prefrontal cortex (PFC). In this context, the D1 receptor activation level in the prefrontal cortex should be regulated at the optimum to perform a working memory task. Because the regulation of the optimal D1 receptor activation in the PFC depends on the dopamine release in the PFC, controlling the dopamine release and the activity of the mesofrontal dopaminergic neurons must be necessary to acquire accurate working memory activity of the cortical neurons. Based on the neuroanatomical findings, we have recently shown that this closed-loop system can regulate working memory activity in the prefrontal cortex by stabilized optimum dopamine release. We here report our recent study which is designed to investigate computationally 1) qualitative and quantitative aspects of the dynamics of the fronto-mesofrontal system; and 2) functional difference in regulation of frontal dopamine release between the fronto-mesofrontal system and the tonic disinhibitory circuit. [Jpn J Physiol 55 Suppl:S57 (2005)]