Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice
Cell Reports. 2023-10-01; 42(10): 113287
DOI: 10.1016/j.celrep.2023.113287
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Delgado-Zabalza L(1), Mallet NP(2), Glangetas C(2), Dabee G(2), Garret M(3), Miguelez C(4), Baufreton J(5).
Author information:
(1)University Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France; Department
of Pharmacology. University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
(2)University Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France.
(3)University Bordeaux, CNRS, INCIA, UMR 5287, 33000 Bordeaux, France.
(4)Department of Pharmacology. University of the Basque Country (UPV/EHU), 48940
Leioa, Spain; Autonomic and Movement Disorders Unit, Neurodegenerative Diseases,
Biocruces Health Research Institute, Barakaldo, Spain.
(5)University Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France. Electronic
address: .
The activity of substantia nigra pars reticulata (SNr) neurons, the main output
structure of basal ganglia, is altered in Parkinson’s disease (PD). However,
neither the underlying mechanisms nor the type of neurons responsible for
PD-related motor dysfunctions have been elucidated yet. Here, we show that
parvalbumin-expressing SNr neurons (SNr-PV+) occupy dorsolateral parts and
possess specific electrophysiological properties compared with other SNr cells.
We also report that only SNr-PV+ neurons’ intrinsic excitability is reduced by
downregulation of sodium leak channels in a PD mouse model. Interestingly, in
anesthetized parkinsonian mice in vivo, SNr-PV+ neurons display a bursty pattern
of activity dependent on glutamatergic tone. Finally, we demonstrate that
chemogenetic inhibition of SNr-PV+ neurons is sufficient to alleviate motor
impairments in parkinsonian mice. Overall, our findings establish
cell-type-specific dysfunction in experimental parkinsonism in the SNr and
provide a potential cellular therapeutic target to alleviate motor symptoms in
PD.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.