Real-time measurements of neurotransmitters are critical for understanding how chemical signaling is controlled in the brain and how it malfunctions during neurological diseases. Regulation of neurotransmission occurs on a millisecond time scale but monitoring neurotransmitter concentrations has been instrumentally limited to the second to minute time scale. Neurotransmitter measurements require both high temporal resolution and high sensitivity, as nanomolar concentration changes are expected. The goal of this research is to develop high sensitivity, high temporal resolution electrochemical sensors to understand the regulation of dopamine concentrations on a millisecond time scale. The strategy is to fabricate high sensitivity carbon nanotube (CNT) yarn and CNT fiber microelectrodes for high temporal resolution measurements with fast-scan cyclic voltammetry (FSCV). FSCV provides both a fingerprint for identification of the species being detected and high temporal resolution. However, the scan is usually repeated at 100 ms intervals with traditional carbon-fiber microelectrodes because sensitivity decreases with increasing repetition rate. Preliminary data show that CNT yarn and CNT fiber microelectrodes do not suffer from this drawback and can be used with rapid repetition rates. The CNT microelectrodes are expected to provide a 1 nM limit of detection with 2 ms temporal resolution, which is sufficient to characterize dopamine release after single stimulation pulses in vivo for the first time. The firs aim is to study CNT fibers as microelectrode materials. The fibers are made by wet spinning techniques, by extruding CNTs into a coagulant such as polyethyleneimine.
The second aim i s to test CNT yarns as microelectrode sensors. CNT yarns are a commercial material that is made by twisting aligned CNT arrays into aligned CNT yarns. For both CNT yarn and CNT fiber microelectrodes, the effects of oxide functionalization on adsorption and electrochemical properties will be studied. The best sensors will be used to characterize dopamine release in vivo to show that they are useful for high temporal resolution measurements in a biological sample. The ability to measure release from a single stimulation pulse will enable the hypothesis that the interval between single stimulations during burst firing regulates the amount of dopamine release to be tested. This work is significant because it will overcome a critical instrumentation barrier for monitoring dopamine release and allow the first characterization of dopamine on the millisecond time scale, 50-times faster than currently possible. This will open the door for future studies of how millisecond regulation of dopamine impacts diseases, such as addiction. These sensors could also be implemented to monitor other electroactive compounds including adenosine, serotonin, norepinephrine, histamine, ascorbic acid, and hydrogen peroxide. Thus, the potential impact is a better understanding of the millisecond regulation of many neurotransmitters and neuromodulators.
The proposed research is relevant to public health because the characterization of the dopamine and other neurotransmitter signaling is ultimately expected to lead to a better understanding of how neurotransmission is regulated and how that changes during diseases. New sensors for high temporal resolution measurements will allow an unprecedented picture of real-time changes in neurotransmitters. Thus, the proposed research is relevant to the NIH's mission to develop fundamental knowledge about the nature of living systems that can be applied to reduce the burdens of illness.
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