Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

We have previously established that PV+ neurons and Npas1(+) neurons are distinct neuron classes in the external globus pallidus (GPe): they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2+ neurons, which are a unique subclass within the Npas1(+) class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes. By using these novel driver lines, we have provided the most exhaustive investigation of electrophysiological studies of GPe neuron subtypes to date. Corroborating our prior studies, GPe neurons can be divided into two statistically distinct clusters that map onto PV+ and Npas1(+) classes. By combining optogenetics and machine learning-based tracking, we showed that optogenetic perturbation of GPe neuron subtypes generated unique behavioral structures. Our findings further highlighted the dissociable roles of GPe neurons in regulating movement and anxiety-like behavior. We concluded that Npr3(+) neurons and Kcng4(+) neurons are distinct subclasses of Npas1(+) neurons and PV+ neurons, respectively. Finally, by examining local collateral connectivity, we inferred the circuit mechanisms involved in the motor patterns observed with optogenetic perturbations. In summary, by identifying mouse lines that allow for manipulations of GPe neuron subtypes, we created new opportunities for interrogations of cellular and circuit substrates that can be important for motor function and dysfunction.

Automated summary

By using novel driver lines, this study provides an exhaustive investigation of electrophysiological studies of GPe neuron subtypes, revealing that Npr3(+) neurons and Kcng4(+) neurons are distinct subclasses of Npas1(+) and PV+ neurons, respectively. Through optogenetics and machine learning-based tracking, unique behavioral structures generated by optogenetic perturbation of GPe neuron subtypes were observed, highlighting the dissociable roles of GPe neurons in regulating movement and anxiety-like behavior.