title: Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements.
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.
authors.affiliation: Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki 444-8585, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Chiken
authors.affiliation: Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara 252-0374, Japan National Institute for Basic Biology, Okazaki 444-8585, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Sato
authors.affiliation: Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohta
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kurokawa
authors.affiliation: Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara 252-0374, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Arai
authors.affiliation: Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara 252-0374, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeshima
authors.affiliation: National Institute for Basic Biology, Okazaki 444-8585, Japan Department of Life Sciences, Graduate School of Arts and Science, The University of Tokyo, Tokyo 153-8902, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sunayama-Morita
authors.affiliation: School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki 444-8585, Japan Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara 252-0374, Japan National Institute for Basic Biology, Okazaki 444-8585, Japan Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Toshikuni
authors.initials: T
authors.lastname: Sasaoka
authors.affiliation: Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki 444-8585, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nambu
mesh_terms: D000818:Animals; D004318:Doxycycline / Q000494:pharmacology; D004558:Electric Stimulation; D020392:Entopeduncular Nucleus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009044:Motor Cortex / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D045442:Rotarod Performance Test
chemical_list: D017447:Receptors, Dopamine D1; D004318:Doxycycline
keywords: basal ganglia; conditional knockdown; dopamine receptor; extracellular recording; mouse