VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors

Author:

Baek Soo Ji12,Park Jin Sung12,Kim Jinhyun12,Yamamoto Yukio1ORCID,Tanaka-Yamamoto Keiko12ORCID

Affiliation:

1. Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST)

2. Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST)

Abstract

Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of the cerebellum to stress symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the development of chronic stress-induced behavioral alterations in mice. Chronic chemogenetic activation of inhibitory Purkinje cells in crus I suppressed c-Fos expression in the DN and an increase in immobility in the tail suspension test or forced swimming test, which were triggered by chronic stress application. The combination of adeno-associated virus-based circuit mapping and electrophysiological recording identified network connections from crus I to the VTA via the dentate nucleus (DN) of the deep cerebellar nuclei. Furthermore, chronic inhibition of specific neurons in the DN that project to the VTA prevented stressed mice from showing such depression-like behavior, whereas chronic activation of these neurons alone triggered behavioral changes that were comparable with the depression-like behaviors triggered by chronic stress application. Our results indicate that the VTA-projecting cerebellar neurons proactively regulate the development of depression-like behavior, raising the possibility that cerebellum may be an effective target for the prevention of depressive disorders in human.

Funder

National Research Foundation of Korea

Korea Institute of Science and Technology

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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