The cerebellum directly modulates the substantia nigra dopaminergic activity

Document Type

Article

Publication Date

3-1-2024

Abstract

Evidence of direct reciprocal connections between the cerebellum and basal ganglia has challenged the long-held notion that these structures function independently. While anatomical studies have suggested the presence of cerebellar projections to the substantia nigra pars compacta (SNc), the nature and function of these connections (Cb–SNc) is unknown. Here we show, in mice, that Cb–SNc projections form monosynaptic glutamatergic synapses with dopaminergic and non-dopaminergic neurons in the SNc. Optogenetic activation of Cb–SNc axons in the SNc is associated with increased SNc activity, elevated striatal dopamine levels and increased locomotion. During behavior, Cb–SNc projections are bilaterally activated before ambulation and unilateral lever manipulation. Cb–SNc projections show prominent activation for water reward and higher activation for sweet water, suggesting that the pathway also encodes reward value. Thus, the cerebellum directly, rapidly and effectively modulates basal ganglia dopamine levels and conveys information related to movement initiation, vigor and reward processing.

Identifier

85182990033 (Scopus)

Publication Title

Nature Neuroscience

External Full Text Location

https://doi.org/10.1038/s41593-023-01560-9

e-ISSN

15461726

ISSN

10976256

PubMed ID

38272967

First Page

497

Last Page

513

Issue

3

Volume

27

Grant

S10OD025295

Fund Ref

National Institutes of Health

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