Year: 2023
Type: article
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 "bridging" collaterals within the globus pallidus (GPe), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches to dissect the roles of bridging 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 pallidostriatal Npas1 neurons. We propose a model by which dSPN GPe collaterals ("striatopallidal Go pathway") act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 signals going back to the striatum.
Source: Nature Communications
Institutions: University of Zurich, Columbia University Irving Medical Center, ETH Zurich, New York State Psychiatric Institute, Columbia University, Barnard College, National Institute on Drug Abuse, Universitat de Barcelona, Johns Hopkins University, Johns Hopkins Medicine, Northwestern University, Weizmann Institute of Science
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: National Science Foundation, Brain and Behavior Research Foundation, AstraZeneca, European Molecular Biology Organization, Leon Levy Foundation, Novartis Foundation, National Alliance for Research on Schizophrenia and Depression, Philippe Foundation, Branco Weiss Fellowship – Society in Science, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Israel Science Foundation, China Scholarship Council, Novartis Stiftung für Medizinisch-Biologische Forschung, National Institutes of Health, Horizon 2020 Framework Programme, Neuroscience Center Zurich, University of Zurich, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, H2020 European Research Council
Awards: G2201577057, Training in Schizophrenia and Psychotic Disorders: From Animal Models to Patients, G3230583274, Diagenese und Geochemie von Sandsteinen, G4242830897, Reevaluating classical models of basal ganglia circuits: neuronal targets and behavioral significance of axonal collaterals bridging the direct and indirect pathways, Reevaluating classical models of basal ganglia circuits: neuronal targets and behavioral significance of axonal collaterals bridging the direct and indirect pathways, G4794521972, G5614821604, G59496374, G657093227, G673330677, G7127356040, G728184197, Organization and learning-associated dynamics of prefrontal synaptic connectivity, G7478274618, G818275612, Neural signals programming energy balance in the mouse basal ganglia, G9000193048, Co-Regulation of Striatal Dopamine and Acetylcholine During Flexible Learning, PRIMING THE PUMP: TRAINING PHYSICIAN-SCIENTISTS IN TRANSLATIONAL PSYCHIATRY
OpenAlex ID: W4387880714