Disruption of Cortical Dopaminergic Modulation Impairs Preparatory Activity and Delays Licking Initiation

Cereb Cortex. 2019 Apr 1;29(4):1802-1815. doi: 10.1093/cercor/bhz005.


Dysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson's disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of head-fixed mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemilesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemilesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked, and preparatory activity in ALM, and licking initiation.

Keywords: 6-hydroxydopamine; Parkinson’s disease; dopamine; licking; motor cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cues
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Motor Cortex / drug effects
  • Motor Cortex / metabolism*
  • Mouth
  • Oxidopamine
  • Parkinsonian Disorders / metabolism*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism


  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Oxidopamine
  • Dopamine