This proposal is directed at the development and use of dynamic chemical measurements to determine the mechanisms of neurotransmission in the brain. Information is transferred between neurons by small molecules known as neurotransmitters. These molecules are secreted by neurons as a result of an integration of the inputs to that cell. The transmitters then diffuse to adjacent cells where they interact with specific receptors and cause biochemical changes which lead to further neuronal integration. The progress in the previously funded periods has resulted in the first method which is capable of providing a real-time, spatially localized view of any neurotransmitter directly in the intact brain. The method employs rapid electrochemical measurements with a carbon-fiber microelectrode and provides chemically selective measurements of dopamine for the determination of the kinetics, mechanism, and regulation of neurotransmission. This proposal details plans to improve the technology, and to use it to further characterize dopamine neuro transmission. In addition, we will extend the technique to the study of 5.hydroxytryptamine (5-HT), another biogenic amine neurotransmitter, and will develop new types of chemical sensors specifically designed for the detection of chemical communication between cells.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Heetderks, William J
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University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
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Dankoski, Elyse C; Carroll, Susan; Wightman, Robert Mark (2016) Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release. J Neurochem 136:1131-1141
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Dankoski, Elyse C; Agster, Kara L; Fox, Megan E et al. (2014) Facilitation of serotonin signaling by SSRIs is attenuated by social isolation. Neuropsychopharmacology 39:2928-37
Park, Jinwoo; Bucher, Elizabeth S; Fontillas, Khristy et al. (2013) Opposing catecholamine changes in the bed nucleus of the stria terminalis during intracranial self-stimulation and its extinction. Biol Psychiatry 74:69-76
McElligott, ZoƩ A; Fox, Megan E; Walsh, Paul L et al. (2013) Noradrenergic synaptic function in the bed nucleus of the stria terminalis varies in animal models of anxiety and addiction. Neuropsychopharmacology 38:1665-73
Herr, Natalie Rios; Wightman, Robert Mark (2013) Improved techniques for examining rapid dopamine signaling with iontophoresis. Front Biosci (Elite Ed) 5:249-57
Hashemi, Parastoo; Dankoski, Elyse C; Lama, Rinchen et al. (2012) Brain dopamine and serotonin differ in regulation and its consequences. Proc Natl Acad Sci U S A 109:11510-5

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