Deep Brain Stimulation of the Medial Septal Nucleus Induces Expression of a Virally Delivered Reporter Gene in Dentate Gyrus

Frontiers in Neuroscience

Darrin J. Lee¹  Suneil K. Kalia¹  Lorraine V. Kalia²  Andres M. Lozano²  Clement Hamani³  Eun Jung Lee⁴  Mitchell L. de Snoo⁴  Anton Fomenko⁴  Elise Gondard⁴  Clemens Neudorfer⁴  Chris McKinnon⁴ 

[1] Department of Neurological Surgery and USC Neurorestoration Center, Keck School of Medicine of USC, Los Angeles, CA, United States;Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada;Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada;Krembil Research Institute, University Health Network, Toronto, ON, Canada;

关键词: neuromodulation;    deep brain stimulation;    viral vector;    gene expression;    medial septal nucleus;    hippocampus;   

DOI  :  10.3389/fnins.2020.00463

来源: DOAJ

【 摘 要 】

BackgroundMechanisms 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.ObjectiveThis 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.MethodsRats 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.ResultsNo 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.ConclusionWe 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.

【 授权许可】

Unknown