Aberrant Cerebellar-Recipient Thalamic Activity in Two Mouse Models with Prominent Tremor or Bradykinesia

Area of Science:

• Neuroscience
• Motor Control
• Parkinson's Disease Pathophysiology

Background:

• The motor thalamus is crucial for motor control, connecting subcortical and cortical areas.
• Distinct thalamic sub-circuits receive input from the basal ganglia and cerebellum.
• Parkinson's disease involves dopamine loss and alpha-synuclein aggregation, affecting motor function.

Purpose of the Study:

• To investigate how motor thalamic sub-circuits are altered in mouse models of Parkinson's disease.
• To compare pathophysiology in cerebellar-recipient (CBMT) and basal ganglia-recipient (BGMT) motor thalamus territories.
• To differentiate effects of alpha-synuclein aggregation versus dopamine loss.

Main Methods:

• Utilized trans-synaptic viral tracing to delineate CBMT and BGMT in mice.
• Studied two Parkinson's disease models: 3K alpha-synuclein aggregation and 6-OHDA dopamine depletion.
• Employed in vivo electrophysiology to record neuronal activity and movement-related responses.

Main Results:

• In the 3K model (tremor phenotype), pathophysiology was confined to the CBMT.
• In the 6-OHDA model (bradykinesia phenotype), pathophysiology affected both CBMT and BGMT.
• Both models showed irregular CBMT neuronal activity with dampened movement responses; 6-OHDA also reduced CBMT baseline firing.

Conclusions:

• Parkinson's disease pathophysiology selectively impacts the motor thalamus.
• Alpha-synucleinopathy primarily affects cerebellar-recipient thalamic circuits.
• Dopamine loss leads to more global thalamic dysfunction involving both cerebellar and basal ganglia inputs.