Parvalbumin⁺ and Npas1⁺ Pallidal Neurons Have Distinct Circuit Topology and Function

Area of Science:

• Neuroscience
• Motor Control
• Basal Ganglia Circuitry

Background:

• The external globus pallidus (GPe) is a crucial component of the basal ganglia, implicated in motor control.
• Altered GPe neuron activity is observed in Parkinson's disease (PD), suggesting its role in motor dysfunction.
• The GPe comprises distinct neuron classes, including parvalbumin-positive (PV+) and Npas1+ neurons, with different properties but unclear functional roles in movement.

Purpose of the Study:

• To establish the causal relationship between distinct GPe neuron classes and motor control.
• To investigate the differential synaptic influences on GPe neuron types from the subthalamic nucleus (STN).
• To explore alterations in GPe-STN circuitry in a Parkinson's disease model.

Main Methods:

• Optogenetic techniques were employed in male and female mice to manipulate PV+ and Npas1+ neuron activity.
• Electrophysiological recordings and lesion models (6-hydroxydopamine) were used to study synaptic connectivity and PD-related changes.

Main Results:

• Optogenetic activation of PV+ neurons promoted locomotion, while activation of Npas1+ neurons suppressed it.
• PV+ and Npas1+ neurons receive distinct synaptic inputs from the STN.
• A selective weakening of STN inputs to PV+ neurons was observed in the PD model.

Conclusions:

• PV+ and Npas1+ neurons in the GPe exert opposing, causal influences on locomotion.
• Differential STN connectivity to GPe neuron types shapes motor output.
• Impaired STN-GPe circuitry, particularly reduced STN input to PV+ neurons, may underlie hypokinetic symptoms in Parkinson's disease, providing targets for future therapies.