Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements

Cereb Cortex. 2015 Dec;25(12):4885-97. doi: 10.1093/cercor/bhv209. Epub 2015 Oct 6.


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.

Keywords: basal ganglia; conditional knockdown; dopamine receptor; extracellular recording; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Doxycycline / pharmacology
  • Electric Stimulation
  • Entopeduncular Nucleus / drug effects
  • Entopeduncular Nucleus / physiology*
  • Female
  • Gene Knockdown Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity* / drug effects
  • Motor Cortex / physiology*
  • Neural Inhibition / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D1 / physiology*
  • Rotarod Performance Test


  • Receptors, Dopamine D1
  • Doxycycline