Data from: Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing

The role of striatal pathways in cognitive processing is unclear. We
studied dorsomedial striatal cognitive processing during interval timing,
an elementary cognitive task that requires mice to estimate intervals of
several seconds and involves working memory for temporal rules as well as
attention to the passage of time. We harnessed optogenetic tagging to
record from striatal D2- dopamine receptor-expressing medium spiny neurons
(D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing
MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs
exhibited distinct dynamics over temporal intervals as quantified by
principal component analyses and trial-by-trial generalized linear models.
MSN recordings helped construct and constrain a four-parameter
drift-diffusion computational model in which MSN ensemble activity
represented the accumulation of temporal evidence. This model predicted
that disrupting either D2-MSNs or D1-MSNs would increase interval timing
response times and alter MSN firing. In line with this prediction, we
found that optogenetic inhibition or pharmacological disruption of either
D2-MSNs or D1-MSNs increased interval timing response times.
Pharmacologically disrupting D2-MSNs or D1-MSNs also changed MSN dynamics
and degraded trial-by-trial temporal decoding. Together, our findings
demonstrate that D2-MSNs and D1-MSNs had opposing dynamics yet played
complementary cognitive roles, implying that striatal direct and indirect
pathways work together to shape temporal control of action. These data
provide novel insight into basal ganglia cognitive operations beyond
movement and have implications for human striatal diseases and therapies
targeting striatal pathways.