Prefrontal - subthalamic pathway supports action selection in a spatial working memory task

Sci Rep. 2020 Jun 26;10(1):10497. doi: 10.1038/s41598-020-67185-1.


Subthalamic nucleus (STN) is the main source of feed-forward excitation in the basal ganglia and a main target of therapeutic deep brain stimulation in movement disorders. Alleviation of motor symptoms during STN stimulation can be accompanied by deterioration of abilities to quickly choose between conflicting alternatives. Cortical afferents to the subthalamic region (ST), comprising STN and zona incerta (ZI), include projections from the medial prefrontal cortex (mPFC), yet little is known about prefrontal-subthalamic coordination and its relevance for decision-making. Here we combined electrophysiological recordings with optogenetic manipulations of projections from mPFC to ST in mice as they performed a spatial working memory task (T-maze) or explored an elevated plus maze (anxiety test). We found that gamma oscillations (30-70 Hz) are coordinated between mPFC and ST at theta (5-10 Hz) and, less efficiently, at sub-theta (2-5 Hz) frequencies. An optogenetic detuning of the theta/gamma cross-frequency coupling between the regions into sub-theta range impaired performance in the T-maze, yet did not affect anxiety-related behaviors in the elevated plus maze. Both detuning and inhibition of the mPFC-ST pathway led to repeated incorrect choices in the T-maze. These effects were not associated with changes of anxiety and motor activity measures. Our findings suggest that action selection in a cognitively demanding task crucially involves theta rhythmic coordination of gamma oscillatory signaling in the prefrontal-subthalamic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gamma Rhythm / physiology
  • Maze Learning / physiology
  • Memory, Short-Term / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Optogenetics / methods
  • Prefrontal Cortex / physiology*
  • Spatial Memory / physiology*
  • Subthalamic Nucleus / physiology*
  • Theta Rhythm / physiology