Direct in Vivo Electrochemical Detection of Resting Dopamine Using Poly(3,4-ethylenedioxythiophene)/Carbon Nanotube Functionalized Microelectrodes

Dopamine (DA) is a monoamine neurotransmitter responsible for the maintenance of a variety of vital life functions. In vivo DA signaling occurs over multiple time scales, from subsecond phasic release due to dopamine neuron firing to tonic release responsible for long-term DA concentration changes over minutes to hours. Due to the complex, multifaceted nature of DA signaling, analytical sensing technology must be capable of recording DA from multiple locations and over multiple time scales. Decades of research has focused on improving in vivo detection capabilities for subsecond phasic DA, but the accurate detection of absolute resting DA levels in real time has proven challenging. We have developed a poly(3,4-ethylenedioxythiophene) (PEDOT)-based nanocomposite coating that exhibits excellent DA sensing capabilities for resting DA. PEDOT/ functionalized carbon nanotube (PEDOT/CNT)-coated carbon fiber microelectrodes (CFEs) are capable of directly measuring resting DA using square wave voltammetry (SWV) with high sensitivity and selectivity. Incorporation of a PEDOT/CNT coating significantly increases the sensitivity for the detection of resting DA by a factor of 422. SWV measurements performed at PEDOT/CNT-functionalized CFEs implanted in the rat dorsal striatum reveal the absolute basal DA concentration to be 82 ± 6 nM. Systemic administration of the dopamine transporter inhibitor nomifensine increases resting DA to a maximum 207 ± 16 nM at 28 ± 2 min following injection. PEDOT/CNT was also functionalized onto individual gold electrode sites along silicon microelectrode arrays (MEAs) to produce a multisite DA sensing electrode. MEA resolution. SWV detection paired with PEDOT/CNT functionalization is highly adaptable and shows great promise for tonic DA detection with high spatial and temporal resolution. Abstract Tonic and phasic dopamine (DA) neurotransmission are responsible for the regulation of a myriad of vital life functions. 1–6 Phasic DA release induces transient, subsecond fluctuations in extracellular DA, whereas tonic firing maintains basal DA levels that serve to regulate phasic firing. 7,8 It is widely believed that preserving tonic and phasic firing is key to maintaining healthy neuronal functionality. Dysfunction in the regulation of tonic and phasic DA firing has been implicated in the onset of devastating neurological disorders, such as schizophrenia. 6 As such, it is absolutely necessary to consider both tonic and phasic DA signaling events when studying DA signaling pathways. DA is an electroactive compound capable of reversible oxidation to upon application of sufficient Electrochemical measurement of real-time, Fast scan cyclic fiber dorsal detection of resting DA in vitro via differential pulse voltammetry. 43 In this study we incorporate PEDOT/CNT coatings onto both implantable CFEs and gold electrode sites along single-shank silicon-based microelectrode arrays (MEAs) to produce a highly adaptable and robust new electrode technology. Pairing PEDOT/CNT-functionalized microelectrodes in an array with a highly optimized in vivo square wave voltammetry (SWV) protocol allows for the direct quantification of resting (tonic) DA in the rat with excellent spatial and temporal resolution. The power of this technology is clearly evident in the results of a proof-of-principle experiment detailing the first reported time-correlated, multisite quantification of basal DA in the brain by recording at multiple PEDOT/CNT-functionalized electrode sites along a single silicon MEA. Multisite detection of in vivo resting DA represents a substantial improvement in the current state of the art of neurochemical sensing and could serve to enhance our understanding of healthy and disease state neurological function.