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Cerebellum Directly Modulates the Substantia Nigra Dopaminergic Activity

View ORCID ProfileSamantha Washburn, View ORCID ProfileMaritza Oñate, View ORCID ProfileJunichi Yoshida, View ORCID ProfileJorge Vera, View ORCID ProfileRamakrishnan K. B., View ORCID ProfileLeila Khatami, View ORCID ProfileFarzan Nadim, View ORCID ProfileKamran Khodakhah
doi: https://doi.org/10.1101/2022.05.20.492532
Samantha Washburn
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Maritza Oñate
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Junichi Yoshida
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Jorge Vera
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Ramakrishnan K. B.
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Leila Khatami
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Farzan Nadim
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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Kamran Khodakhah
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York.
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  • ORCID record for Kamran Khodakhah
  • For correspondence: k.khodakhah@einsteinmed.edu
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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 that the Cb-SNc form monosynaptic glutamatergic synapses with both dopaminergic and non-dopaminergic neurons in the SNc. Optogenetic activation Cb-SNc axons in the SNc rapidly increases SNc activity, elevates striatal dopamine levels, and increases the probability of locomotion. During ongoing behavior, Cb-SNc axons are bilaterally activated prior to ambulation and unilateral lever manipulation. The Cb-SNc axons show prominent activation to 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 possibly reward processing.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 22, 2022.
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Cerebellum Directly Modulates the Substantia Nigra Dopaminergic Activity
Samantha Washburn, Maritza Oñate, Junichi Yoshida, Jorge Vera, Ramakrishnan K. B., Leila Khatami, Farzan Nadim, Kamran Khodakhah
bioRxiv 2022.05.20.492532; doi: https://doi.org/10.1101/2022.05.20.492532
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Cerebellum Directly Modulates the Substantia Nigra Dopaminergic Activity
Samantha Washburn, Maritza Oñate, Junichi Yoshida, Jorge Vera, Ramakrishnan K. B., Leila Khatami, Farzan Nadim, Kamran Khodakhah
bioRxiv 2022.05.20.492532; doi: https://doi.org/10.1101/2022.05.20.492532

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