Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing.

Area of Science:

• Neuroscience
• Cognitive Science
• Computational Neuroscience

Background:

• The precise function of striatal pathways in cognitive processes remains largely unknown.
• Interval timing, a fundamental cognitive task, relies on working memory and attention, with the striatum implicated in its execution.

Purpose of the Study:

• To investigate the role of dorsomedial striatal pathways, specifically D1-MSN and D2-MSN populations, in interval timing.
• To elucidate the distinct dynamics and complementary functions of direct and indirect striatal pathways in temporal cognition.

Main Methods:

• Utilized optogenetic tagging to record from D1-MSNs and D2-MSNs in mice during an interval timing task.
• Employed principal component analyses and generalized linear models to analyze MSN activity dynamics.
• Developed and constrained a drift-diffusion computational model using MSN recordings to represent temporal evidence accumulation.

Main Results:

• D1-MSNs and D2-MSNs displayed distinct activity dynamics over temporal intervals.
• Disrupting either D1-MSNs or D2-MSNs via optogenetics or pharmacology increased response times in interval timing.
• Pharmacological disruption altered MSN dynamics and impaired trial-by-trial temporal decoding.

Conclusions:

• D1-MSNs and D2-MSNs exhibit opposing dynamics but play complementary roles in interval timing.
• The direct and indirect striatal pathways cooperate to regulate the temporal control of actions.
• Findings offer new insights into basal ganglia cognitive functions and have implications for striatal diseases.