Enhancing technologies to simultaneously measure the concentration of monoamines across small areas of the brain

Alterations in the release or uptake of neuromodulators such as dopamine, norepinephrine and serotonin have been implicated in several neurological disorders including schizophrenia, depression and Parkinson‘s disease. Voltammetry is a method used to measure the concentration of neuromodulators in-vivo with good temporal (sub-second) and spatial (sub-micron) resolution and has been used to study release and uptake. By applying a potential difference across two electrodes, the neuromodulators of interest is oxidized and the resulting oxidation current is proportional to the concentration of the neuromodulators. Recent voltammetry studies suggested that the concentration of neuromodulators varies within small regions of the brain, and since neural function differs within small regions of the brain, a change in the concentration of neuromodulators may have significant impact on neural processing. We have been particularly interested in the role of monoamines, especially norepinephrine (NE), in the primary somatosensory cortex (SI). To assess the heterogeneity of the noradrenergic uptake transporter, we compared the change in concentration of monoamines in-vivo to computer simulations of diffusion and uptake (Chapter 1). To improve the technology for recording from multi-sites simultaneously, we developed a multi-channel voltammetry system and studied the effect of different carbon deposition techniques on electrode performance (Chapter 2). This work demonstrated the first multichannel in-vivo voltammetry system that can record simultaneously from multiple working electrodes. Finally, we used voltammetry to determine if stimulus induced release of NE, via electrical stimulation of the LC, can be detected in the primary somatosensory cortex of the rat (Chapter 3). The in-vivo studies identified a spatial heterogeneity of NE uptake in the primary somatosensory cortex after exogenous release of neurotransmitters into the extracellular space. Stimulus-evoked release of endogenous NE was recorded in the primary somatosensory cortex and the effect of the psychostimulant methylphenidate (Ritalin) was studied. Data demonstrate that methylphenidate blocked the uptake of NE and decreased the release. This work lays the foundation to study the release and uptake of norepinephrine and drugs that modulate its regulation in the primary somatosensory cortex in the rat.Ph.D., Biomedical Engineering -- Drexel University, 200