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Short latency cerebellar modulation of the basal ganglia

Nature Neuroscience volume 17, pages 17671775 (2014) | Download Citation

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Abstract

The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia.

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Acknowledgements

We thank the members of the Khodakhah laboratory for invaluable discussions and comments on the manuscript. This work was supported by grants from the US National Institutes of Health (NS050808, NS079750 and NS071665).

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  1. Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.

    • Christopher H Chen
    • , Rachel Fremont
    • , Eduardo E Arteaga-Bracho
    •  & Kamran Khodakhah

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Contributions

The studies were initiated by K.K. and C.H.C., who designed the bulk of the experiments. C.H.C. performed all of the experiments except for those shown in Figure 8. R.F. designed and performed the experiments shown in Figure 8. E.E.A.-B. and C.H.C. designed and performed the experiments shown in Figures 6 and 7. All of the authors contributed to writing the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Kamran Khodakhah.

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    Alleviation of cerebellar-induced dystonia by optogenetic inactivation of the thalamic intralaminar nuclei.

    ArchT was expressed in the intralaminar nuclei targeting CL, and dystonia was induced by infusion of ouabain into the cerebellum. Inactivation of the thalamus rapidly abated symptoms.

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https://doi.org/10.1038/nn.3868

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