PROJECT SUMMARY/ABSTRACT
Mental disorders, such as depression, anxiety, and many others, affect the quality of life of millions of people
worldwide. High-molecular-weight neurochemicals, such as neuropeptides and other polypeptide
neurochemicals, play critical roles in various aspects of these mental disorders. However, despite intensive work,
current measurement technologies, such as microdialysis or cyclic voltammetry, lack the spatial and temporal
precision and the molecular specificity to detect these larger molecules. Our long-term goal is to develop
advanced tools and approaches to understand where, when, and how neuropeptide corelease modulates diverse
behavioral outputs of the brain. Our immediate goal is to develop, optimize, benchmark, and fully validate a
wireless, multimodal neural probe for simultaneous membrane-free neurochemical sampling and
neuropharmacology in freely moving mice and rats. We will achieve this goal by pursuing the following three
specific aims: (1) to develop and characterize a push-pull microsystem for membrane-free neurochemical
sampling; (2) to develop a wireless, multimodal neural probe for simultaneous membrane-free neurochemical
sampling and neuropharmacology; and (3) to evaluate and characterize the efficiency and functionality of the
wireless, multimodal neural probe in vivo in freely moving mice and rats. The proposed research is innovative
for four key reasons: First, the wireless neural probe combines the membrane-free, push-pull microsystem with
a time-sequential fluid sampling device, thereby enabling the sampling of multiple neuropeptides and proteins
with spatiotemporal precision. Second, the probe provides simultaneous neuropharmacology and membrane-
free neurochemical sampling in awake, freely moving mice and rats, thereby making it possible to sample
multiple high-molecular-weight neurochemicals and in turn guide localized pharmacological stimulation through
a single platform. Third, the fully wireless, battery-free operation prevents the limitations that conventional wires
and tubing connected to external hardware impose on the natural behavior of animals, thereby offering a
tremendous opportunity to link neuromodulation and/or neurochemical release with natural animal behaviors
related to mental disorders. Finally, the probe has lightweight construction, thereby enabling the application in
small animals, such as mice, without inducing physical stress or disrupting their natural behaviors, a condition
important for behavior studies related to mental disorders. The successful completion of the proposed research
will yield wireless, multimodal neural probes with several innovative features for simultaneous membrane-
free neurochemical sampling and neuropharmacology during freely moving behaviors. We believe that these
neural probe systems will be of great interest to the neuroscience community as a way of elucidating the
molecular mechanisms underlying aberrant behavior, circuit dysfunction and altered neurochemistry associated
with mental disorders.
