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

Area of Science:

• Neuroscience
• Motor Control Research
• Computational Neuroscience

Background:

• Coordinated motor behavior relies on information flow between brain regions.
• The specific mechanisms by which long-range inputs modulate cell-type-specific activity in motor circuits are not fully understood.
• The dorsolateral striatum (DLS) comprises direct-pathway medium spiny neurons (dMSNs) and indirect-pathway medium spiny neurons (iMSNs), known to have distinct roles in movement regulation.

Purpose of the Study:

• To investigate how cortical and thalamic inputs drive cell-type-specific activity within the DLS during skilled locomotion.
• To identify functional subpopulations within dMSNs, iMSNs, and their projecting inputs.
• To elucidate the complementary roles of corticostriatal and thalamostriatal pathways in motor control.

Main Methods:

• Monosynaptic rabies tracing to identify inputs to dMSNs and iMSNs.
• In vivo electrophysiological recordings in mice performing skilled locomotion.
• Recurrent neural network (RNN) classification and clustering analysis to identify neuronal subpopulations and activity patterns.
• Inactivation of cortical or thalamic regions to assess their impact on MSN activity.

Main Results:

• Functional heterogeneity was observed in dMSNs, iMSNs, and their inputs, with dMSNs activated at movement onset/offset and iMSNs during execution.
• Cortical inputs were preferentially active during movement onset/offset, while thalamic inputs were active during execution.
• Locomotion phase-specific rhythmic activity was detected in a subset of thalamic dMSN-projecting neurons and dMSNs.
• Inactivation of the cortex or thalamus led to reduced MSN activity.

Conclusions:

• Corticostriatal and thalamostriatal inputs provide distinct, complementary motor signals to the DLS.
• These signals are conveyed through pathways that are both shared and cell-type-specific, targeting dMSNs and iMSNs.
• Understanding these pathways is crucial for deciphering the neural basis of coordinated motor behavior.