Effect of Deep Brain Stimulation in The Ventral Tegmental Area on Neuronal Activity in Local and Remote Brain Regions in Kindled Mice

Document Type : Original Article


1 Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands

3 Department of Physiology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia

4 Institute for Brain Sciences and Cognition, Tarbiat Modares University, Tehran, Iran


Objective: The mechanisms behind seizure suppression by deep brain stimulation (DBS) are not fully revealed, and
the most optimal stimulus regimens and anatomical targets are yet to be determined. We investigated the modulatory
effect of low-frequency DBS (L-DBS) in the ventral tegmental area (VTA) on neuronal activity in downstream
and upstream brain areas in chemically kindled mice by assessing c-Fos immunoreactivity.
Materials and Methods: In this experimental study, 4-6 weeks old BL/6 male mice underwent stereotaxic implantation
of a unilateral stimulating electrode in the VTA followed by pentylenetetrazole (PTZ) administration every other day
until they showed stage 4 or 5 seizures following 3 consecutive PTZ injections. Animals were divided into control,
sham-implanted, kindled, kindled-implanted, L-DBS, and kindled+L-DBS groups. In the L-DBS and kindled+L-DBS
groups, four trains of L-DBS were delivered 5 min after the last PTZ injection. 48 hours after the last L-DBS, mice were
transcardially perfused, and the brain was processed to evaluate c-Fos expression by immunohistochemistry.
Results: L-DBS in the VTA significantly decreased the c-Fos expressing cell numbers in several brain areas including
the hippocampus, entorhinal cortex, VTA, substantia nigra pars compacta, and dorsal raphe nucleus but not in the
amygdala and CA3 area of the ventral hippocampus compared to the sham group.
Conclusion: These data suggest that the possible anticonvulsant mechanism of DBS in VTA can be through restoring
the seizure-induced cellular hyperactivity to normal.


Main Subjects

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