The cerebellum directly modulates the substantia nigra dopaminergic activity

Samantha Washburn, Maritza Oñate, Junichi Yoshida, Jorge Vera, Ramakrishnan Bhuvanasundaram, Leila Khatami, Farzan Nadim, Kamran Khodakhah

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)497-513
Number of pages17
JournalNature Neuroscience
Volume27
Issue number3
DOIs
StatePublished - Mar 2024

All Science Journal Classification (ASJC) codes

  • General Neuroscience

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