Optogenetic activation of striatal D1R and D2R cells differentially engages downstream connected areas beyond the basal ganglia

Christina Grimm; Stefan Frässle; Céline Steger; Lukas von Ziegler; Oliver Sturman; Noam Shemesh; Daria Peleg-Raibstein; Denis Burdakov; Johannes Bohacek; Klaas Enno Stephan; Daniel Razansky; Nicole Wenderoth; Valerio Zerbi

doi:10.1016/j.celrep.2021.110161

Optogenetic activation of striatal D1R and D2R cells differentially engages downstream connected areas beyond the basal ganglia

Cell Rep. 2021 Dec 28;37(13):110161. doi: 10.1016/j.celrep.2021.110161.

Authors

Affiliations

¹ Neural Control of Movement Lab, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zurich, ETH Zürich and University of Zurich, Zürich, Switzerland.
² Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Zürich, Switzerland.
³ Neuroscience Center Zurich, ETH Zürich and University of Zurich, Zürich, Switzerland; Center for MR Research, University Children's Hospital Zurich, Zürich, Switzerland.
⁴ Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zurich, ETH Zürich and University of Zurich, Zürich, Switzerland.
⁵ Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal.
⁶ Laboratory of Neurobehavioral Dynamics, Department of Health Sciences and Technology, Institute for Neuroscience, ETH Zürich, Zürich, Switzerland; Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zürich, Switzerland.
⁷ Laboratory of Neurobehavioral Dynamics, Department of Health Sciences and Technology, Institute for Neuroscience, ETH Zürich, Zürich, Switzerland; Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zürich, Switzerland; Neuroscience Center Zurich, ETH Zürich and University of Zurich, Zürich, Switzerland.
⁸ Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zürich, Zürich, Switzerland; Institute of Biological and Medical Imaging (IBMI), Technical University of Munich and Helmholtz Center Munich, Munich, Germany; Neuroscience Center Zurich, ETH Zürich and University of Zurich, Zürich, Switzerland.
⁹ Neural Control of Movement Lab, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zurich, ETH Zürich and University of Zurich, Zürich, Switzerland. Electronic address: valerio.zerbi@hest.ethz.ch.

PMID: 34965430
DOI: 10.1016/j.celrep.2021.110161

Abstract

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However, whether they maintain a uniform function across the striatum and what influence they exert outside the BG is unclear. Here, we address these questions by combining optogenetic activation of D1R and D2R cells in the mouse ventrolateral caudoputamen with fMRI. Striatal D1R/D2R stimulation evokes distinct activity within the BG-thalamocortical network and differentially engages cerebellar and prefrontal regions. Computational modeling of effective connectivity confirms that changes in D1R/D2R output drive functional relationships between these regions. Our results suggest a complex functional organization of striatal D1R/D2R cells and hint toward an interconnected fronto-BG-cerebellar network modulated by striatal D1R and D2R cells.

Keywords: D1R/D2R; basal ganglia; brain networks; caudate putamen; direct/indirect pathway; fMRI; movement disorders; opto-fMRI; optogenetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basal Ganglia / metabolism*
Corpus Striatum / metabolism*
Female
Male
Mice
Neostriatum / metabolism*
Neurons / metabolism*
Optogenetics*
Receptors, Dopamine D1 / metabolism*
Receptors, Dopamine D2 / metabolism*

Substances

Receptors, Dopamine D1
Receptors, Dopamine D2