Fast Analytical Sensing Technology (FAST)
Applications: We are currently using in vivo electrochemistry in order to address a number of translational research projects. First, we are studying the effects of altered glutamate neurotransmission in aging, epilepsy, spinal cord injury and neurodegenerative diseases. We are also interested in how glutamate neurotransmission is regulated in awake behaving animal models during behavioral events. Secondly, we continue to be involved in understanding the effects of aging on the function of midbrain dopamine neurons. By combining in vivo electrochemical measurements of dopamine release and clearance with biochemical markers of dopamine neurons, we are beginning to understand how movement disorders may relate to changes in the functional properties of midbrain dopamine cells. In addition, we are assessing glutamate and dopamine function in animal models of Parkinson's disease, in order to better understand how this illness affects various properties of glutamate and dopamine release and clearance. Our work to create a microelectrode recording array having select coatings allows us to now accurately measure resting levels of glutamate and dopamine in both anesthized and awake animal models on a sub-second basis. In addition, we are developing other microelectrodes for second-by-second measures of oxygen, lactate, aspartate, glucose, alcohol, adenosine, choline, acetylcholine and other molecules. We are also developing methodology for the simultaneous recording of LFP’s with electrochemical recordings. The studies outlined here, as well as many others, are being carried out in collaboration with other researchers from around the world.
In vivo electrochemistry relies on the fact that certain compounds can undergo oxidation (electron loss) or reduction (electron gain) reactions at a given applied potential. During such a reaction, the number of molecules of a substance is directly related to the number of electrons detected. Moreover, these reactions can be reliably detected on millisecond time scales, and on small surfaces. In our laboratory, we take advantage of the principles of electrochemistry in order to detect a variety of electroactive compounds in the brain. The Fast Analytical Sensing Technology (FAST) system, developed at the CenMeT, allows us to accurately detect compounds such as glutamate, choline, dopamine, norepinephrine, Serotonin, and nitric oxide with high sensitivity (< 10 nM) and on a short (< 1 s) time scale.
Measurements are carried out on ceramic-based microelectrode arrays (MEA’s) or carbon fiber sensors, the dimensions of which are small enough to penetrate the extra cellular space of the brain with only minimal tissue disruption. A small potential (0.55, 0.7 or 0.9 V relative to a standard AgCl reference) is applied to the surface of the electrode, thereby causing oxidation of the electroactive species at the surface of the electrode. The current generated by this reaction is converted to an actual concentration change (for example, on a µM scale), based on standard curves generated prior to each experiment. These signals can be generated many times per second and are typically displayed every second, so that a "real time" assessment of the electrochemical signal can be seen. The signal parameters obtained in these recordings, such as peak height and time to decay, can be used to define properties of neuronal release and reuptake. For example, it is possible to detect dopamine release in several brain regions using a variety of known physiologic stimuli. Moreover, agents that are known to affect release or reuptake, such as amphetamine or cocaine, will alter the parameters of the electrochemical signal. In this way, it is possible to study the dynamic processes of neuronal function in the intact animal.
- Accurate In vivo detection of compounds such as glutamate, choline, lactate, glucose, dopamine, norepinephrine, serotonin, nitric oxide and oxygen
- with high sensitivity (< 10 nM for DA; < 0.5 µM for Glu)
- on a short (< 1 s) time scale
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