(Invited) New Platforms for Multiplexing Electrochemical Measurements In Vivo
Authors: Heien Michael Leandro 
Published: February 2020

Complex behaviors depend on the coordination of the activities of ensembles of neurons and the release of neuromodulators such as dopamine. The mechanisms underlying such coordination are not well-understood due to a lack of instrumentation for combined and real-time monitoring of neuromodulator release and the activities of large ensembles of neurons. Here I describe a measurement platform that allows for the combined monitoring of electrophysiology from a high-density electrode array and dopamine dynamics from a carbon-fiber microelectrode. Integration of these two measurement systems was achieved through modification of the existing instrumentation. A shared grounded reference electrode was used in both systems to minimize electrical interference. Further, an optional solid-state-relay array positioned between the electrophysiological electrode array and amplifiers was added to provide additional electrical isolation. The capacity of the integrated measurement platform, termed DANA (Dopamine And Neural Activity), to measure action potentials (high frequency) and local-field oscillations (low frequency) was characterized in vitro using an artificial cerebral spinal fluid gelatin. In vivo recordings from the DANA platform in anesthetized rats demonstrated the ability of the system for near-simultaneous measurement of dopamine release and activity from multiple neurons both in distant brain regions (striatum and hippocampus) and within the same brain region (striatum). Furthermore, this system was shown to be sufficiently compact to measure activity in freely moving animals through recording of single-neuron activity, high-frequency local-field oscillations, and dopamine release.
Fast scan cyclic voltammetry has been used extensively to monitor dynamic changes in neurotransmitters (e.g. dopamine, serotonin, norepinephrine) in real time. However, these measurements are limited in terms of the number of implantable sensors. This does not allow the coordinated chemical communication and interactions between groups of neurons to be mapped in the same animal. Additioanally, we present arrays of electrodes with biocompatible conducting polymers capable of measuring biogenic amines. Metal wires are coated with the electrochemical polymerization of the monomer 3,4-ethylenedioxythiophene (EDOT). After baking and rinsing, a film with a positively charged polymer backbone balanced by negatively charged tosylate ions is formed. These electrodes can then be easily integrated in mass-producible arrays, brining voltammetry on par with multiple probe recordings common in electrophysiology. These voltammetric recordings also require custom instrumentation that integrates low-noise operational amplifiers with high-performance data acquisition cards and software. The system presented is capable of recording from eight channels (with appropriate instrumentation). By electrically isolating each channel, they can be independently addressed and a different neurotransmitter can be measured at each sensor. This greatly increases the ability to map neurotransmitter release in the brain of animals in real time. Data measuring both dopamine and serotonin in different brain regions is presented.