Journal article
Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing
eLife, Vol.13, RP96287
01/15/2025
DOI: 10.7554/eLife.96287.4
Abstract
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.
Details
- Title: Subtitle
- Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing
- Creators
- Robert A Bruce - University of IowaMatthew Weber - University of Iowa, NeurologyAlexandra Bova - University of Iowa, NeurologyRachael Volkman - University of Iowa, NeurologyCasey Jacobs - University of IowaKartik Sivakumar - University of Iowa, NeurologyHannah Stutt - University of IowaYoungcho Kim - University of Iowa, NeurologyRodica Curtu - University of Iowa, Iowa Neuroscience InstituteKumar Narayanan - University of Iowa, Iowa Neuroscience Institute
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.13, RP96287
- DOI
- 10.7554/eLife.96287.4
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Language
- English
- Date published
- 01/15/2025
- Academic Unit
- Neurology; Mathematics; Iowa Neuroscience Institute
- Record Identifier
- 9984801203102771
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