Complementary Contributions of Striatal Projection Pathways to Action Initiation and Execution

• Published in: Cell Vol. 166; no. 3; pp. 703 - 715
• Main Authors: Tecuapetla, Fatuel, Jin, Xin, Lima, Susana Q., Costa, Rui M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28-07-2016
• Subjects: Animals; Basal Ganglia - physiology; Corpus Striatum - cytology; Corpus Striatum - physiology; Male; Mice; Mice, Inbred C57BL; Models, Neurological; Movement; Neural Pathways - physiology; Neurons - physiology; Optogenetics; Psychomotor Performance - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2016.06.032

The performance of an action relies on the initiation and execution of appropriate movement sequences. Two basal ganglia pathways have been classically hypothesized to regulate this process via opposing roles in movement facilitation and suppression. By using a series of state-dependent optogenetic manipulations, we dissected the contributions of each pathway and found that both the direct striatonigral pathway and the indirect striatopallidal pathway are necessary for smooth initiation and the execution of learned action sequences. Optogenetic inhibition or stimulation of each pathway before sequence initiation increased the latency for initiation: manipulations of the striatonigral pathway activity slowed action initiation, and those of the striatopallidal pathway aborted action initiation. The inhibition of each pathway after initiation also impaired ongoing execution. Furthermore, the subtle activation of striatonigral neurons sustained the performance of learned sequences, while striatopallidal manipulations aborted ongoing performance. These results suggest a supportive versus permissive model, where patterns of coordinated activity, rather than the relative amount of activity in these pathways, regulate movement initiation and execution.
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•Both basal ganglia pathways are required for action sequence initiation and performance•Striatonigral manipulations slowed, but striatopallidal manipulations aborted, initiation•Striatonigral, but not striatopallidal, pathway activation prolonged action sequences•Inhibition or overactivation of the striatopallidal pathway aborted action sequences
The direct and the indirect basal ganglia pathway regulate movements by acting in complementary supportive and permissive manners, rather than by having opposing hyperkinetic and akinetic effects.