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 clas...
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| Published in: | The Journal of neuroscience Vol. 41; no. 18; p. 4036 |
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| Language: | English |
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| 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 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.
Within the basal ganglia, the external globus pallidus (GPe) has long been recognized for its involvement in motor control. However, we lacked an understanding of precisely how movement is controlled at the GPe level as a result of its cellular complexity. In this study, by using transgenic and cell-specific approaches, we showed that genetically-defined GPe neuron subtypes have distinct roles in regulating motor patterns. In addition, the
contributions of these neuron subtypes are in part shaped by the local, inhibitory connections within the GPe. In sum, we have established the foundation for future investigations of motor function and disease pathophysiology. |
|---|---|
| AbstractList | 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.
Within the basal ganglia, the external globus pallidus (GPe) has long been recognized for its involvement in motor control. However, we lacked an understanding of precisely how movement is controlled at the GPe level as a result of its cellular complexity. In this study, by using transgenic and cell-specific approaches, we showed that genetically-defined GPe neuron subtypes have distinct roles in regulating motor patterns. In addition, the
contributions of these neuron subtypes are in part shaped by the local, inhibitory connections within the GPe. In sum, we have established the foundation for future investigations of motor function and disease pathophysiology. 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.SIGNIFICANCE STATEMENT Within the basal ganglia, the external globus pallidus (GPe) has long been recognized for its involvement in motor control. However, we lacked an understanding of precisely how movement is controlled at the GPe level as a result of its cellular complexity. In this study, by using transgenic and cell-specific approaches, we showed that genetically-defined GPe neuron subtypes have distinct roles in regulating motor patterns. In addition, the in vivo contributions of these neuron subtypes are in part shaped by the local, inhibitory connections within the GPe. In sum, we have established the foundation for future investigations of motor function and disease pathophysiology.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.SIGNIFICANCE STATEMENT Within the basal ganglia, the external globus pallidus (GPe) has long been recognized for its involvement in motor control. However, we lacked an understanding of precisely how movement is controlled at the GPe level as a result of its cellular complexity. In this study, by using transgenic and cell-specific approaches, we showed that genetically-defined GPe neuron subtypes have distinct roles in regulating motor patterns. In addition, the in vivo contributions of these neuron subtypes are in part shaped by the local, inhibitory connections within the GPe. In sum, we have established the foundation for future investigations of motor function and disease pathophysiology. |
| Author | Chen, Yi Abecassis, Zachary A Boca, Simina M Xenias, Harry S Zhang, Yu Rajamanickam, Shivakumar Wilson, Charles J Berceau, Brianna L Higgs, Matthew H Justice, Nicholas J McMorrow, Hayley Du, Xixun Cherian, Suraj Chang, Isaac Y M Chan, C Savio Cui, Qiaoling Pamukcu, Arin |
| Author_xml | – sequence: 1 givenname: Qiaoling surname: Cui fullname: Cui, Qiaoling organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 2 givenname: Arin surname: Pamukcu fullname: Pamukcu, Arin organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 3 givenname: Suraj surname: Cherian fullname: Cherian, Suraj organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 4 givenname: Isaac Y M surname: Chang fullname: Chang, Isaac Y M organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 5 givenname: Brianna L surname: Berceau fullname: Berceau, Brianna L organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 6 givenname: Harry S orcidid: 0000-0002-9502-0973 surname: Xenias fullname: Xenias, Harry S organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 7 givenname: Matthew H surname: Higgs fullname: Higgs, Matthew H organization: Department of Biology, University of Texas at San Antonio, San Antonio 78249, Texas – sequence: 8 givenname: Shivakumar surname: Rajamanickam fullname: Rajamanickam, Shivakumar organization: Department of Integrative Pharmacology, University of Texas, Houston 77030, Texas – sequence: 9 givenname: Yi surname: Chen fullname: Chen, Yi organization: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison 53706, Wisconsin – sequence: 10 givenname: Xixun surname: Du fullname: Du, Xixun organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 11 givenname: Yu surname: Zhang fullname: Zhang, Yu organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 12 givenname: Hayley surname: McMorrow fullname: McMorrow, Hayley organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 13 givenname: Zachary A surname: Abecassis fullname: Abecassis, Zachary A organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois – sequence: 14 givenname: Simina M surname: Boca fullname: Boca, Simina M organization: Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington 20057, DC – sequence: 15 givenname: Nicholas J surname: Justice fullname: Justice, Nicholas J organization: Department of Integrative Pharmacology, University of Texas, Houston 77030, Texas – sequence: 16 givenname: Charles J surname: Wilson fullname: Wilson, Charles J organization: Department of Biology, University of Texas at San Antonio, San Antonio 78249, Texas – sequence: 17 givenname: C Savio orcidid: 0000-0002-3474-1718 surname: Chan fullname: Chan, C Savio email: saviochan@gmail.com organization: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago 60611, Illinois saviochan@gmail.com |
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| Keywords | body kinematics behavioral dynamics reciprocal inhibition machine learning local collaterals arkypallidal neurons |
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| Snippet | We have previously established that PV
neurons and Npas1
neurons are distinct neuron classes in the external globus pallidus (GPe): they have different... We have previously established that PV+ neurons and Npas1+ neurons are distinct neuron classes in the external globus pallidus (GPe): they have different... |
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| SubjectTerms | Animals Anxiety - psychology Basic Helix-Loop-Helix Transcription Factors - genetics Behavior, Animal Biomechanical Phenomena Electrophysiological Phenomena Female Globus Pallidus - cytology Globus Pallidus - physiology Machine Learning Male Mice Mice, Inbred C57BL Motor Activity - physiology Nerve Net - cytology Nerve Net - physiology Nerve Tissue Proteins - genetics Neurons - physiology Optogenetics Potassium Channels, Voltage-Gated - genetics Receptors, Atrial Natriuretic Factor - genetics |
| Title | Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns |
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