The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior.
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http://dx.doi.org/10.1126/science.aav0581 | DOI Listing |
Am J Psychiatry
January 2025
Department of Neuroscience, Medical University of South Carolina, Charleston (Kuhn, Crow, Walterhouse, Chalhoub, Dereschewitz, Roberts, Kalivas); School of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, Italy (Cannella, Lunerti, Ciccocioppo); Interdisciplinary Ph.D. Program in Biostatistics (Gupta) and Department of Biomedical Informatics (Gupta, Allen, Chung), and Pelotonia Institute for Immuno-Oncology, James Comprehensive Cancer Center, Ohio State University, Columbus (Gupta, Allen, Chung); Department of Internal Medicine, Wake Forest University, Winston-Salem, NC (Cockerham, Beeson, Solberg Woods); Department of Psychology, Jacksonville State University, Jacksonville, AL (Nall); Institute for Genomic Medicine, University of California San Diego, La Jolla (Palmer); School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland (Hardiman).
Objective: The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting the translational relevance of the mechanistic research that is conducted in experimental animals. The authors hypothesized that a nonlinear clustering of OUD-like behavioral traits would capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles.
Methods: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors.
Contemp Clin Trials Commun
February 2025
Dept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA.
Background: In people with substance use disorders (SUDs), stress-exposure can impair executive function, and increase craving and likelihood of drug-use recurrence. Research shows that acute stressors increase drug-seeking behavior; however, mechanisms underlying this effect are incompletely understood. The Competing Neurobehavioral Decisions System theory posits that persons with SUDs may have hyperactive limbic reward circuitry and hypoactive executive control circuitry.
View Article and Find Full Text PDFFront Nutr
December 2024
Department of Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China.
Objective: The ventral tegmental area (VTA), a pivotal hub in the brain's reward circuitry, receives inputs from the lateral hypothalamic area (LHA). However, it remains unclear whether melanin-concentrating hormone (MCH) and orexin-A (OX-A) neurons in the LHA exert individual or cooperative influence on palatable food consumption in the VTA. This study aims to investigate the modulatory role of MCH and OX-A in hedonic feeding within the VTA of high-fat diet (HFD) mice.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA.
Front Psychol
December 2024
Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Neurosciences de Lyon U1028 UMR5292, PSYR2, Bron, France.
Background: Anhedonia, including social, physical, and less-known, olfactory, stands as a core symptom of major depressive disorder (MDD). At the neurobiological level, anhedonia has been associated with abnormal activity within the reward system, suggesting a key role for dopamine. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as an innovative treatment for alleviating depressive symptoms.
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