2015.10.13
Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements
（Cerebral Cortex, December 2015;25: 4885-4897 doi: 10.1093/cercor/bhv209）
Satomi Chiken1,2,†, Asako Sato3,4,†, Chikara Ohta1,5, Makoto Kurokawa5, Satoshi Arai3, Jun Maeshima3, Tomoko Sunayama-Morita4,6, Toshikuni Sasaoka2,3,4,7, and Atsushi Nambu1,2
†These authors contributed equally to this work.
1Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan,
2School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki 444-8585, Japan,
3Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara 252-0374, Japan,
4National Institute for Basic Biology, Okazaki 444-8585, Japan,
5Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan,
6Department of Life Sciences, Graduate School of Arts and Science, The University of Tokyo, Tokyo 153-8902, Japan
7Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University
Abstract
In the basal ganglia (BG), dopamine plays a pivotal role in motor control, and dopamine deficiency results in severe motor dysfunctions as seen in Parkinson's disease. According to the well-accepted model of the BG, dopamine activates striatal direct pathway neurons that directly project to the output nuclei of the BG through D1 receptors (D1Rs), whereas dopamine inhibits striatal indirect pathway neurons that project to the external pallidum (GPe) through D2 receptors. To clarify the exact role of dopaminergic transmission via D1Rs in vivo, we developed novel D1R knockdown mice in which D1Rs can be conditionally and reversibly regulated. Suppression of D1R expression by doxycycline treatment decreased spontaneous motor activity and impaired motor ability in the mice. Neuronal activity in the entopeduncular nucleus (EPN), one of the output nuclei of the rodent BG, was recorded in awake conditions to examine the mechanism of motor deficits. Cortically evoked inhibition in the EPN mediated by the cortico-striato-EPN direct pathway was mostly lost during suppression of D1R expression, whereas spontaneous firing rates and patterns remained unchanged. On the other hand, GPe activity changed little. These results suggest that D1R-mediated dopaminergic transmission maintains the information flow through the direct pathway to appropriately release motor actions.
