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Abstract
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.
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Details
1 Medical Faculty, Heinrich-Heine-University Düsseldorf, Institute of Clinical Neuroscience and Medical Psychology, Düsseldorf, Germany (GRID:grid.411327.2) (ISNI:0000 0001 2176 9917)
2 Instituto Cajal, CSIC, Department of Functional and Systems Neurobiology, Madrid, Spain (GRID:grid.419043.b) (ISNI:0000 0001 2177 5516)
3 Max Planck Institute for Metabolism Research, Cologne, Germany (GRID:grid.418034.a) (ISNI:0000 0004 4911 0702); University of Cologne, Institute for Vegetative Physiology, Medical Faculty, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777)
4 Medical Faculty, Heinrich-Heine-University Düsseldorf, Institute of Clinical Neuroscience and Medical Psychology, Düsseldorf, Germany (GRID:grid.411327.2) (ISNI:0000 0001 2176 9917); Friedrich-Alexander-University Erlangen-Nürnberg, Institute of Physiology and Pathophysiology, Erlangen, Germany (GRID:grid.5330.5) (ISNI:0000 0001 2107 3311)