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Nat Neurosci. 2017 Jun;20(6):815-823. doi: 10.1038/nn.4559. Epub 2017 May 8.

Cell-specific pallidal intervention induces long-lasting motor recovery in dopamine-depleted mice.

Author information

1
Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
2
Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
3
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

The identification of distinct cell types in the basal ganglia has been critical to our understanding of basal ganglia function and the treatment of neurological disorders. The external globus pallidus (GPe) is a key contributor to motor suppressing pathways in the basal ganglia, yet its neuronal heterogeneity has remained an untapped resource for therapeutic interventions. Here we demonstrate that optogenetic interventions that dissociate the activity of two neuronal populations in the GPe, elevating the activity of parvalbumin (PV)-expressing GPe neurons over that of Lim homeobox 6 (Lhx6)-expressing GPe neurons, restores movement in dopamine-depleted mice and attenuates pathological activity of basal ganglia output neurons for hours beyond stimulation. These results establish the utility of cell-specific interventions in the GPe to target functionally distinct pathways, with the potential to induce long-lasting recovery of movement despite the continued absence of dopamine.

PMID:
28481350
PMCID:
PMC5546121
DOI:
10.1038/nn.4559
[Indexed for MEDLINE]
Free PMC Article

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