A non-canonical striatopallidal Go pathway that supports motor control

Marie A. Labouesse; Arturo Torres-Herraez; Muhammad O. Chohan; Joseph M. Villarin; Julia Greenwald; Xiaoxiao Sun; Mysarah Zahran; Alice Tang; Sherry Lam; Jeremy Veenstra-VanderWeele; Clay O. Lacefield; Jordi Bonaventura; Michael Michaelides; C. Savio Chan; Ofer Yizhar; Christoph Kellendonk

doi:10.1038/s41467-023-42288-1

A non-canonical striatopallidal Go pathway that supports motor control

Marie A. Labouesse^*, Arturo Torres-Herraez, Muhammad O. Chohan, Joseph M. Villarin, Julia Greenwald, Xiaoxiao Sun, Mysarah Zahran, Alice Tang, Sherry Lam, Jeremy Veenstra-VanderWeele, Clay O. Lacefield, Jordi Bonaventura, Michael Michaelides, C. Savio Chan, Ofer Yizhar, Christoph Kellendonk^*

^*Corresponding author for this work

Neuroscience

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.

Original language	English (US)
Article number	6712
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-42288-1
State	Published - Dec 2023

Funding

The study was funded by the NIMH (R01 MH093672, R01 MH124858 to C.K.), the Swiss National Science Foundation (SNSF) (P2EZP3_168841, P400PB_180841 to M.A.L.), NINDS (R01/R56 NS069777 to C.S.C.), NIDA (ZIA000069 to MM) and the Philippe Foundation (awarded in 2017, 2018 to M.A.L.). M.A.L. is supported by an Ambizione Grant from the SNSF (PZ00P3_193430), a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (30854), a Young Investigator Grant from the Novartis Foundation for Medical-Biological Research (22B097), and Research Grants from the Vontobel Stiftung (1334_2021), the Olga-Mayenfisch Stiftung (awarded in 2022) and the Neuroscience Center Zurich (awarded in 2021). A.T.H. is supported by the European Molecular Biology Organization (ALTF 561-2020), J.V. by the Leon Levy Foundation (awarded in 2017) and the NIMH (T32MH018870) and J.B. by the MICIN (RYC2019-027371-I and PID2020-117989RA-I00). O.Y. is supported by the European Research Council (819496), the EU Horizon2020 program (H2020-ICT-2018-20 DEEPER 101016787) and by the Israel Science Foundation (3131/20). We thank C. Labouesse, T. Rahbek-Clemmensen, S. Gershbaum, G. Stevens, B. Rao and M. Billiard for advice with analysis or scripts, A. Cebula, J. Sherman and J. Baer for technical assistance and S. Modica (ETHZ VVPP) and M. Mahn for help with construct design/cloning and AAV production. Figures A, E; A, C; A, A, D; A, D, E; A, A, C, D; A, C, H; ; S; S; S; S were created with BioRender.com.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-023-42288-1

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Labouesse, M. A., Torres-Herraez, A., Chohan, M. O., Villarin, J. M., Greenwald, J., Sun, X., Zahran, M., Tang, A., Lam, S., Veenstra-VanderWeele, J., Lacefield, C. O., Bonaventura, J., Michaelides, M., Chan, C. S., Yizhar, O., & Kellendonk, C. (2023). A non-canonical striatopallidal Go pathway that supports motor control. Nature communications, 14(1), Article 6712. https://doi.org/10.1038/s41467-023-42288-1

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title = "A non-canonical striatopallidal Go pathway that supports motor control",

abstract = "In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.",

author = "Labouesse, {Marie A.} and Arturo Torres-Herraez and Chohan, {Muhammad O.} and Villarin, {Joseph M.} and Julia Greenwald and Xiaoxiao Sun and Mysarah Zahran and Alice Tang and Sherry Lam and Jeremy Veenstra-VanderWeele and Lacefield, {Clay O.} and Jordi Bonaventura and Michael Michaelides and Chan, {C. Savio} and Ofer Yizhar and Christoph Kellendonk",

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year = "2023",

month = dec,

doi = "10.1038/s41467-023-42288-1",

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Labouesse, MA, Torres-Herraez, A, Chohan, MO, Villarin, JM, Greenwald, J, Sun, X, Zahran, M, Tang, A, Lam, S, Veenstra-VanderWeele, J, Lacefield, CO, Bonaventura, J, Michaelides, M, Chan, CS, Yizhar, O & Kellendonk, C 2023, 'A non-canonical striatopallidal Go pathway that supports motor control', Nature communications, vol. 14, no. 1, 6712. https://doi.org/10.1038/s41467-023-42288-1

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T1 - A non-canonical striatopallidal Go pathway that supports motor control

AU - Labouesse, Marie A.

AU - Torres-Herraez, Arturo

AU - Chohan, Muhammad O.

AU - Villarin, Joseph M.

AU - Greenwald, Julia

AU - Sun, Xiaoxiao

AU - Zahran, Mysarah

AU - Tang, Alice

AU - Lam, Sherry

AU - Veenstra-VanderWeele, Jeremy

AU - Lacefield, Clay O.

AU - Bonaventura, Jordi

AU - Michaelides, Michael

AU - Chan, C. Savio

AU - Yizhar, Ofer

AU - Kellendonk, Christoph

PY - 2023/12

Y1 - 2023/12

N2 - In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.

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A non-canonical striatopallidal Go pathway that supports motor control

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