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Complementary cortical and thalamic contributions to cell-type-specific striatal activity dynamics during movement

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Dec 22, 2025 version files 5.19 GB

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Abstract

Coordinated motor behavior emerges from information flow across brain regions. How long-range inputs influence cell-type-specific activity within motor circuits remains unclear. The dorsolateral striatum (DLS) contains direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) that exhibit distinct roles in movement control, and receives converging cortical and thalamic inputs. We performed 2-photon imaging from dMSNs, iMSNs, and their cortical and thalamic inputs identified by monosynaptic rabies tracing, as mice executed a skilled locomotion task. We used recurrent neural network (RNN) classifiers and hierarchical clustering analyses to reveal functionally heterogeneous subpopulations in each population. We found that dMSNs were preferentially active at movement onset and offset, and iMSNs during execution. Cortical and thalamic inputs were preferentially active during onset/offset and execution, respectively. dMSN- and iMSN-projecting neurons in each region showed similar trial-averaged activity patterns, although single-trial features might contribute to cell-type-specific differences. Furthermore, a subset of thalamic neurons projecting to dMSNs encoded rhythmic limb movements in a locomotion phase-specific manner, a pattern also found in a small subset of dMSNs. Inactivation of either cortex or thalamus substantially reduced MSN activity. These results suggest that corticostriatal and thalamostriatal inputs contribute complementary motor-related information via shared and cell-type-specific pathways.