Probing Neural Communication by Expanding In Vivo Electrochemical and Electrophysiological Measurements

Abstract

Neural communication is imperative for physical and mental health. Dysfunction in either ionic signaling or chemical neurotransmission can cause debilitating disorders. Thus, study of neurotransmission is critical not only to answer important fundamental questions regarding learning, decision making, and behavior but also to gain information that can provide insight into the neurochemistry of neurological disorders and lead to improved treatments. The work presented herein describes the development of techniques and instrumentation to enable advancements in neuroscientific inquiry. The effect of different temporal patterns and durations of simulation of the prefrontal cortex on dopamine release in the nucleus accumbens was examined and revealed a complex interaction that can help improve deep brain stimulation therapies. A measurement platform that combines electrophysiological and electrochemical techniques is described. The instrumentation is capable of concurrent monitoring of neural activity and dopamine release in vivo and in freely moving rodents. Analysis techniques to allow absolute quantification of tonic dopamine concentrations in vivo are detailed and the temporal resolution of the technique was vastly improved from ten minutes to forty seconds. An instrument that can simultaneously probe both dopamine and serotonin dynamics in either of their two temporal modes of signaling (tonic and phasic) using either fast-scan cyclic voltammetry or fast-scan controlled-adsorption voltammetry at two individually addressable microelectrodes is described. Together these new tools represent a significant step forward in the field of neuroanalytical chemistry by enable multiple brain regions, signaling modes (ionic flux in addition to both tonic and phasic neurotransmission), neurochemicals, and to be measured together.