This proposal describes a 5 year training program for the development of an academic career in neurosurgery. This program will promote the command of electrophysiology, electrochemistry, brain imaging and stereotactic and functional neurosurgery. Dr. Gary Sieck, Chair of Physiology and Biomedical Engineering, will serve as the primary mentor. A mentorship team of experts in brain imaging, electroanalytical chemistry, neuroengineering and neurosurgery will help the applicant elucidate the mechanisms by which Deep Brain Stimulation (DBS) treats Parkinson's disease. Our recent work demonstrates that subthalamic nucleus (STN) DBS may activate nerve endings to release neurotransmitters, including dopamine. The proposed experiments will entail electrophysiologic, electrochemical, and fluorescent microscopic recordings during DBS.
The specific aims i nclude the demonstration of 1) DBS results in changes in neuronal action potential firing and release of dopamine in the striatum. 2) The therapeutic benefit of STN DBS is mediated by dopamine release in the 6-OH DA lesioned rat model of Parkinson's disease. 3) STN DBS results in release of glutamate in the STN via astrocytic vesicular release mechanism. This study will be the first detailed analysis of the mechanism of DBS as it relates to DBS effect on astrocytic glutamate release and striatal dopamine release. Success in this project will open a new era in medical diagnosis and intervention, providing precise targeting of DBS electrodes and regulation of neurotransmitter that are critically involved in the therapeutic effectiveness of DBS. The applicant, Kendall Lee, M.D., Ph.D., is a new investigator and a neurosurgeon at the Mayo Clinic Rochester with a multidisciplinary background in neurology, neurosurgery, and neuroscience. He has demonstrated the ability to form unique and effective collaborations. To maximize the likelihood of success, the applicant has enlisted as advisors a highly skilled team of researchers: Charles Blaha, Ph.D. (expert in amperometry), Paul Garris, Ph.D. (expert in Parkinson's disease animal models and fast scan cyclic voltammetry), Eric Newman, Ph.D. (expert in astrocyte research), and Demetrius Maragonore, M.D. (Parkinson's disease Neurologist and researcher). In addition, Fredric Meyer, M.D. (Chair, Neurosurgery Mayo Clinic Rochester) will serve as career development advisor, to make certain a successful career in academic neurosurgery for the applicant.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS052232-05
Application #
8286319
Study Section
NST-2 Subcommittee (NST)
Program Officer
Ludwig, Kip A
Project Start
2008-07-01
Project End
2013-12-30
Budget Start
2012-07-01
Budget End
2013-12-30
Support Year
5
Fiscal Year
2012
Total Cost
$182,250
Indirect Cost
$13,500
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Van Gompel, Jamie J; Bower, Mark R; Worrell, Gregory A et al. (2014) Increased cortical extracellular adenosine correlates with seizure termination. Epilepsia 55:233-44
Kasasbeh, Aimen; Lee, Kendall; Bieber, Allan et al. (2013) Wireless neurochemical monitoring in humans. Stereotact Funct Neurosurg 91:141-7
Parpura, Vladimir; Silva, Gabriel A; Tass, Peter A et al. (2013) Neuromodulation: selected approaches and challenges. J Neurochem 124:436-53
Knight, Emily J; Min, Hoon-Ki; Hwang, Sun-Chul et al. (2013) Nucleus accumbens deep brain stimulation results in insula and prefrontal activation: a large animal FMRI study. PLoS One 8:e56640
Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J et al. (2013) Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals. Biol Psychiatry 74:917-26
Pleticha, Josef; Maus, Timothy P; Jeng-Singh, Christian et al. (2013) Pig lumbar spine anatomy and imaging-guided lateral lumbar puncture: a new large animal model for intrathecal drug delivery. J Neurosci Methods 216:10-5
Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J et al. (2013) Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator. Magn Reson Imaging 31:783-8
Jang, Dong Pyo; Kim, Inyong; Chang, Su-Youne et al. (2012) Paired pulse voltammetry for differentiating complex analytes. Analyst 137:1428-35
Chang, Su-Youne; Jay, Taylor; Munoz, Joel et al. (2012) Wireless fast-scan cyclic voltammetry measurement of histamine using WINCS--a proof-of-principle study. Analyst 137:2158-65
Chopra, Amit; Tye, Susannah J; Lee, Kendall H et al. (2012) Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: a review of the literature. J Neuropsychiatry Clin Neurosci 24:102-10

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