Deep Brain Stimulation of the Medial Septal Nucleus Induces Expression of a Virally Delivered Reporter Gene in Dentate Gyrus.
deep brain stimulation
gene expression
hippocampus
medial septal nucleus
neuromodulation
viral vector
Journal
Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481
Informations de publication
Date de publication:
2020
2020
Historique:
received:
17
10
2019
accepted:
15
04
2020
entrez:
2
6
2020
pubmed:
2
6
2020
medline:
2
6
2020
Statut:
epublish
Résumé
Mechanisms of deep brain stimulation (DBS) remain controversial, and spatiotemporal control of brain-wide circuits remains elusive. Adeno-associated viral (AAV) vectors have emerged as vehicles for spatiotemporal expression of exogenous transgenes in several tissues, including specific nuclei in the brain. Coupling DBS with viral vectors to modulate exogenous transgene expression remains unexplored. This study examines whether DBS of the medial septal nucleus (MSN) can regulate gene expression of AAV-transduced neurons in a brain region anatomically remote from the stimulation target: the hippocampal dentate gyrus. Rats underwent unilateral hippocampal injection of an AAV vector with c-Fos promoter-driven expression of TdTomato (TdT), followed by MSN electrode implantation. Rodents received no stimulation, 7.7 Hz (theta), or 130 Hz (gamma) DBS for 1 h one week after surgery. In a repeat stimulation experiment, rodents received either no stimulation, or two 1 h MSN DBS over 2 weeks. No significant differences in hippocampal TdT expression between controls and acute MSN DBS were found. With repeat DBS we found c-Fos protein expression was induced and we could detect increased TdT with either gamma or theta stimulation. We demonstrate that viral vector-mediated gene expression can be regulated spatially and temporally using DBS. Control of gene expression by DBS warrants further investigation into stimulation-responsive promoters for clinical applications.
Sections du résumé
BACKGROUND
BACKGROUND
Mechanisms of deep brain stimulation (DBS) remain controversial, and spatiotemporal control of brain-wide circuits remains elusive. Adeno-associated viral (AAV) vectors have emerged as vehicles for spatiotemporal expression of exogenous transgenes in several tissues, including specific nuclei in the brain. Coupling DBS with viral vectors to modulate exogenous transgene expression remains unexplored.
OBJECTIVE
OBJECTIVE
This study examines whether DBS of the medial septal nucleus (MSN) can regulate gene expression of AAV-transduced neurons in a brain region anatomically remote from the stimulation target: the hippocampal dentate gyrus.
METHODS
METHODS
Rats underwent unilateral hippocampal injection of an AAV vector with c-Fos promoter-driven expression of TdTomato (TdT), followed by MSN electrode implantation. Rodents received no stimulation, 7.7 Hz (theta), or 130 Hz (gamma) DBS for 1 h one week after surgery. In a repeat stimulation experiment, rodents received either no stimulation, or two 1 h MSN DBS over 2 weeks.
RESULTS
RESULTS
No significant differences in hippocampal TdT expression between controls and acute MSN DBS were found. With repeat DBS we found c-Fos protein expression was induced and we could detect increased TdT with either gamma or theta stimulation.
CONCLUSION
CONCLUSIONS
We demonstrate that viral vector-mediated gene expression can be regulated spatially and temporally using DBS. Control of gene expression by DBS warrants further investigation into stimulation-responsive promoters for clinical applications.
Identifiants
pubmed: 32477058
doi: 10.3389/fnins.2020.00463
pmc: PMC7235415
doi:
Types de publication
Journal Article
Langues
eng
Pagination
463Informations de copyright
Copyright © 2020 Fomenko, Lee, McKinnon, Lee, de Snoo, Gondard, Neudorfer, Hamani, Lozano, Kalia and Kalia.
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