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.
