A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced sti...

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Bibliographic Details
Published in:The Journal of physiology 2015-05, Vol.593 (10), p.2257-2278
Main Authors: Arsenault, Dany, Drouin‐Ouellet, Janelle, Saint‐Pierre, Martine, Petrou, Petros, Dubois, Marilyn, Kriz, Jasna, Barker, Roger A., Cicchetti, Antonio, Cicchetti, Francesca
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Aged
Animals
Autopsy
Brain
Brain - physiology
Deep Brain Stimulation - methods
Diagnostic Imaging - methods
Disease Models, Animal
Electrodes
Female
Humans
Luminescent Measurements - methods
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia - physiology
Middle Aged
Motor Cortex - physiology
Neuroscience: Cellular/Molecular
Parkinson Disease - physiopathology
Parkinson's disease
Rodents
Signal Transduction - physiology
Toll-Like Receptor 2 - deficiency
Toll-Like Receptor 2 - genetics
Toll-Like Receptor 2 - physiology
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Summary:Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro‐stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre‐clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll‐like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2‐fluc‐GFP transgenic mice, which we further corroborated with post‐mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.2014.287243