The overall goals of this research program are to develop chemical sensors for compounds of neurochemical importance, and to use these sensors to explore new aspects of brain chemistry. The primary methods that will be used are electroanalytical techniques. These methods can be directly applied for the determination of the easily oxidized biogenic amines. Furthermore, we have shown that the electrodes can be miniaturized for use as in situ probes of the chemical dynamics of neurotransmitter interactions.
The specific aims that will be addressed in this project period are: interactions.
The specific aims that will be addressed in this project period are: 1. The design of electrodes and voltammetric techniques which exhibit increased specificity for neurochemical substances. Work in this area is a continuation of that in the previous proposal and is based on the principle that surface treatment of electrodes can by used to prepare sensors suitable for the determination of neurochemicals. Polymeric coatings will be designed to limit access to the electrode surface of undesired species. Various surface modifications, established in the electroanalytical literature, will be adapted for specific neurochemical substances. An enzyme-based amperometric electrode for acetylcholine will be miniaturized for use in the intact brain. 2. Measurement of chemical changes with micrometer spatial resolution. The microvoltammetric electrodes developed in this laboratory are capable of the determination of concentration changes with considerable spatial resolution. We plan to use this attribute in two applications related to neurochemistry. First, we plan to use carbon fiber electrodes as detectors for compounds separated on conventional high performance columns. The goal of this research is to demonstrate the mechanisms which cause chromatographic bands to be broadened. Second, we plan to use these electrodes to probe the secretion of catecholamines from single, isolated adrenal cells. The high degree of spatial resolution should allow direct measurement of release in real time. 3. Measurement of the dynamics of 5-hydroxytryptamine in brain tissue. During the present project period we have developed a sensitive and selective method for the detection of this neurotransmitter with carbon fiber electrodes. This method will be used to probe the extracellular concentration of this substance both in the brain of anesthetized rats and slices prepared from rat brain tissue. In this way the factors which regulate the actions of 5-hydroxytryptamine will be probed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015841-13
Application #
3396496
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1980-01-01
Project End
1995-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Arts and Sciences
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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
Bucher, Elizabeth S; Wightman, R Mark (2015) Electrochemical Analysis of Neurotransmitters. Annu Rev Anal Chem (Palo Alto Calif) 8:239-61
Fox, Megan E; Studebaker, R Isaac; Swofford, Nathaniel J et al. (2015) Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function. Neuropsychopharmacology 40:1752-61
Dengler, Adam K; Wightman, R Mark; McCarty, Gregory S (2015) Microfabricated Collector-Generator Electrode Sensor for Measuring Absolute pH and Oxygen Concentrations. Anal Chem 87:10556-64
Park, Jinwoo; Bucher, Elizabeth S; Budygin, Evgeny A et al. (2015) Norepinephrine and dopamine transmission in 2 limbic regions differentially respond to acute noxious stimulation. Pain 156:318-27
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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