The cerebellum modulates thirst

Ila Mishra; Bing Feng; Bijoya Basu; Amanda M. Brown; Linda H. Kim; Tao Lin; Mir Abbas Raza; Amelia Moore; Abigayle Hahn; Samantha Bailey; Alaina Sharp; Juan C. Bournat; Claire Poulton; Brian Kim; Amos Langsner; Aaron Sathyanesan; Roy V. Sillitoe; Yanlin He; Atul R. Chopra

doi:10.1038/s41593-024-01700-9

The cerebellum modulates thirst

Ila Mishra, Bing Feng, Bijoya Basu, Amanda M. Brown, Linda H. Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C. Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V. Sillitoe, Yanlin He, Atul R. Chopra

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

5 Scopus citations

Abstract

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin’s dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin–Ptprd signaling may be a potential therapeutic target for the management of thirst disorders.

Original language	English
Pages (from-to)	1745-1757
Number of pages	13
Journal	Nature Neuroscience
Volume	27
Issue number	9
DOIs	https://doi.org/10.1038/s41593-024-01700-9
State	Published - Sep 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

Funding

We thank members of the Chopra lab for helpful suggestions and critical reading of the manuscript. This work was supported by the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK130931, DK118290), the NIH National Institute of Neurological Disorders and Stroke (NINDS) (R01NS119301, R01NS127435), the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD103555) for use of the Cell and Tissue Pathogenesis Core and In Situ Hybridization Core (the BCM IDDRC) and the Harrington Discovery Institute at University Hospitals, Cleveland, Ohio. The Genotype-Tissue Expression (GTEx) Project is supported by the Common Fund of the Office of the Director of the NIH (additional funds were provided by the National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health and NINDS). The use of the Texas A&M Rodent Preclinical Phenotyping Core is acknowledged for the determination of plasma and urine osmolality. The Cardiovascular Research Institute Mouse Metabolic and Phenotyping Core of CWRU (IACUC no. 2019-0029) is acknowledged for the use of metabolic caging.

Funders	Funder number
Baylor College of Medicine, Harrington Investigatorship Harrington Discovery Institute at University Hospitals
National Institute of Mental Health
National Human Genome Research Institute
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse
National Heart, Lung, and Blood Institute Family Blood Pressure Program
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS127435, R01NS119301
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
Eunice Kennedy Shriver National Institute of Child Health and Human Development	P50HD103555
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institute of Diabetes and Digestive and Kidney Diseases	DK118290, DK130931
National Institute of Diabetes and Digestive and Kidney Diseases

ASJC Scopus subject areas

General Neuroscience

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10.1038/s41593-024-01700-9

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title = "The cerebellum modulates thirst",

abstract = "The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin{\textquoteright}s dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by these manipulations, indicating independent control of two divergent functions by Purkinje neurons. Our results show that the cerebellum is a thirst-modulating brain area and that asprosin–Ptprd signaling may be a potential therapeutic target for the management of thirst disorders.",

author = "Ila Mishra and Bing Feng and Bijoya Basu and Brown, \{Amanda M.\} and Kim, \{Linda H.\} and Tao Lin and Raza, \{Mir Abbas\} and Amelia Moore and Abigayle Hahn and Samantha Bailey and Alaina Sharp and Bournat, \{Juan C.\} and Claire Poulton and Brian Kim and Amos Langsner and Aaron Sathyanesan and Sillitoe, \{Roy V.\} and Yanlin He and Chopra, \{Atul R.\}",

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AU - Moore, Amelia

AU - Hahn, Abigayle

AU - Bailey, Samantha

AU - Sharp, Alaina

AU - Bournat, Juan C.

AU - Poulton, Claire

AU - Kim, Brian

AU - Langsner, Amos

AU - Sathyanesan, Aaron

AU - Sillitoe, Roy V.

AU - He, Yanlin

AU - Chopra, Atul R.

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The cerebellum modulates thirst

Abstract

Bibliographical note

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ASJC Scopus subject areas

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