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Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism

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  • Débora Masini

    (University of Copenhagen)

  • Ole Kiehn

    (University of Copenhagen
    Karolinska Institutet)

Abstract

The pedunculopontine nucleus (PPN) is a locomotor command area containing glutamatergic neurons that control locomotor initiation and maintenance. These motor actions are deficient in Parkinson’s disease (PD), where dopaminergic neurodegeneration alters basal ganglia activity. Being downstream of the basal ganglia, the PPN may be a suitable target for ameliorating parkinsonian motor symptoms. Here, we use in vivo cell-type specific PPN activation to restore motor function in two mouse models of parkinsonism made by acute pharmacological blockage of dopamine transmission. With a combination of chemo- and opto-genetics, we show that excitation of caudal glutamatergic PPN neurons can normalize the otherwise severe locomotor deficit in PD, whereas targeting the local GABAergic population only leads to recovery of slow locomotion. The motor rescue driven by glutamatergic PPN activation is independent of activity in nearby locomotor promoting glutamatergic Cuneiform neurons. Our observations point to caudal glutamatergic PPN neurons as a potential target for neuromodulatory restoration of locomotor function in PD.

Suggested Citation

  • Débora Masini & Ole Kiehn, 2022. "Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28075-4
    DOI: 10.1038/s41467-022-28075-4
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    Cited by:

    1. Pan Xu & Yuanlei Yue & Juntao Su & Xiaoqian Sun & Hongfei Du & Zhichao Liu & Rahul Simha & Jianhui Zhou & Chen Zeng & Hui Lu, 2022. "Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Sandeep Sharma & Cecilia A. Badenhorst & Donovan M. Ashby & Stephanie A. Vito & Michelle A. Tran & Zahra Ghavasieh & Gurleen K. Grewal & Cole R. Belway & Alexander McGirr & Patrick J. Whelan, 2024. "Inhibitory medial zona incerta pathway drives exploratory behavior by inhibiting glutamatergic cuneiform neurons," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Li-Ju Hsu & Maëlle Bertho & Ole Kiehn, 2023. "Deconstructing the modular organization and real-time dynamics of mammalian spinal locomotor networks," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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