Abstract
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 Npas11 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.
Original language | English (US) |
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Pages (from-to) | 4036-4059 |
Number of pages | 24 |
Journal | Journal of Neuroscience |
Volume | 41 |
Issue number | 18 |
DOIs | |
State | Published - May 5 2021 |
Funding
This work was supported by National Institutes of Health R01 NS069777, R01 MH112768, R01 NS097901, R01 MH109466, and R01 NS088528 to C.S.C., T32 AG020506 to A.P., T32 NS041234 and F32 NS098793 to H.S.X., R01 MH112768 to N.J.J., R35 NS097185 to C.J.W., and HHMI-PF Medical Research Fellowship and AVA Student Research Fellowship to Z.A.A. We thank Daniela Garcia, Alyssa Bebenek, Moises Melesio, Kris Shah, Ahana Narayanan, Vaishnavi Tetali, Saivasudha Chalasani, and Daniel Hegeman for assistance on the project; Dr. Tiffany Schmidt for providing Kcng4-Cre mice; Dr.
Keywords
- Arkypallidal neurons
- Behavioral dynamics
- Body kinematics
- Local collaterals
- Machine learning
- Reciprocal inhibition
ASJC Scopus subject areas
- General Neuroscience