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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.