Stimulation of the Medial SNr Promotes Sustained Motor Recovery and Counteracts Parkinsonian Pathophysiology in Dopamine Depleted Mice DOI
Asier Aristieta, John E. Parker,

Mary D. Cundiff

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Abstract Dopamine loss alters the activity of neural circuits in basal ganglia, contributing to motor symptoms Parkinson’s disease and catalepsy. Treatments that reduce ganglia pathophysiology alleviate but require maintenance. Cell-type specific interventions can provide sustained therapeutic benefits, a lack understanding pathways involved limits translation. Here, we establish patterns neuromodulation electrophysiological biomarkers at level output predict duration effects. Focal activation neurons ventromedial substantia nigra reticulata (SNr) engaged gradual recovery movement persisted for hours after treatment, accompanied by persistent reduction parkinsonian pathophysiology. Global SNr inhibition, as prescribed classic rate model, provided only transient effects on did not reverse network These findings represent important steps towards developing strategies aim repair, rather than simply mask, circuit dysfunction disease.

Language: Английский

Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses DOI
Alana I. Mendelsohn,

Laudan Nikoobakht,

Jay B. Bikoff

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115454 - 115454

Published: March 27, 2025

Language: Английский

Citations

0
Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses DOI Creative Commons
Alana I. Mendelsohn,

Laudan Nikoobakht,

Jay B. Bikoff

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of output circuits relates molecular diversity cell types. Here, we demonstrate that major nucleus ganglia, substantia nigra pars reticulata (SNr) comprised transcriptomically distinct subclasses reflect its progenitor lineages. We show these are within SNr, project targets in midbrain hindbrain, receive inputs from different striatal subregions. Finally, mouse also identifiable human SNr neurons, suggesting genetic evolutionarily conserved. These findings provide a unifying logic for developmental specification diverse neurons controlling specialized brain regions.

Language: Английский

Citations

1
Stimulation of the Medial SNr Promotes Sustained Motor Recovery and Counteracts Parkinsonian Pathophysiology in Dopamine Depleted Mice DOI
Asier Aristieta, John E. Parker,

Mary D. Cundiff

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Abstract Dopamine loss alters the activity of neural circuits in basal ganglia, contributing to motor symptoms Parkinson’s disease and catalepsy. Treatments that reduce ganglia pathophysiology alleviate but require maintenance. Cell-type specific interventions can provide sustained therapeutic benefits, a lack understanding pathways involved limits translation. Here, we establish patterns neuromodulation electrophysiological biomarkers at level output predict duration effects. Focal activation neurons ventromedial substantia nigra reticulata (SNr) engaged gradual recovery movement persisted for hours after treatment, accompanied by persistent reduction parkinsonian pathophysiology. Global SNr inhibition, as prescribed classic rate model, provided only transient effects on did not reverse network These findings represent important steps towards developing strategies aim repair, rather than simply mask, circuit dysfunction disease.

Language: Английский

Citations

0