Development of an innovative in vivo voltammetric technique for measurements of tonic serotonin concentrations in the mammalian brain.

PROJECT SUMMARY We propose to develop and optimize an advanced neurochemical recording technique that would be able to measure relatively rapid physiologically representative second-to-second changes in tonic concentrations of specific neurochemicals, such as serotonin, in the brains of awake behaving animals. Microdialysis, a commonly used in vivo sampling technique, is able to measure changes that occur in tonic levels. However, in practice the sampling timescale is significantly limited to minute-to-minute changes and it suffers from poor spatial resolution and induces significant tissue damage. Present voltammetry technique can provide tonic measurement capability. However, it raises concerns for accurate quantification due to the limited approach to eliminate background capacitive current. Furthermore, limited biofouling has been shown, limiting its use for long-term tonic serotonin measurements in awake behaving animals. The proposed electrochemical technique we call N-shaped Multiple Cyclic Square Wave Voltammetry (N-MCSWV) will enable second-to-second measurements of tonic extracellular levels of serotonin with exceptional spatial resolution, sensitivity, specificity, selectivity, and diminished biofouling. This proposal leverages our unique expertise in neuroscience, electrochemistry, software development, and engineering to develop and validate this novel neurochemical recording technology for broad use in basic neuroscience research, clinical brain neuromodulation, and a variety of electrochemical applications. Our initial animal studies will guide and inform the application of our investigational technique for use by the general neuroscience and medical community. Our proposal seeks to (1) establish N-MCSWV as a reliable research tool that is capable of identifying and quantifying tonic serotonin extracellular levels in vivo with unsurpassed sensitivity, selectivity, and minimize biofouling, (2) apply Fourier transform electrochemical impedance spectroscopy to N-MCSWV to monitor the degree of electrode biofouling in vivo, and (3) validate the use of N-MCSWV for in vivo, acutely and chronically, selective measurement of tonic serotonin concentrations.