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

Area of Science:

• Neuroscience
• Motor Control
• Systems Neuroscience

Background:

• Coordinated motor behavior relies on information processing across multiple brain regions.
• The specific mechanisms by which long-range inputs influence cell type-specific activity within motor circuits are not fully understood.
• The dorsolateral striatum (DLS), comprising direct-pathway medium spiny neurons (dMSNs) and indirect-pathway medium spiny neurons (iMSNs), plays a critical role in movement control.

Purpose of the Study:

• To investigate how cortical and thalamic inputs modulate the activity of dMSNs and iMSNs during skilled locomotion.
• To identify functionally distinct subpopulations within MSN populations and their input pathways.
• To elucidate the role of corticostriatal and thalamostriatal pathways in conveying motor-related information.

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.
• Inactivation of cortical or thalamic regions.

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 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 complementary motor signals to the DLS.
• These signals are conveyed through both shared and cell type-specific pathways, influencing dMSN and iMSN activity.
• Understanding these pathways is crucial for deciphering the neural basis of skilled motor control.