Functionalized Multi-Modal Tetrode Arrays for Real-Time, Site-Specific Neurochemical Monitoring

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ABSTRACT The goal of this proposal is to develop a multimodal, multianalyte sensor system including wired and wireless electronics and software. This new suite of tools will enable simultaneous recording of amperometric sensors (glutamate, glucose, lactate, choline, and/or oxygen), electrophysiology, and fast-scan cyclic voltammetry (biogenic amines) in conscious, freely moving rodents. The proposed array and measurement system will enable the synchronous measurement of chemical and electrical conditions in the rodent brain. This suite will include new instrumentation and software for simultaneous, synchronized data collection and a novel functionalized tetrode array that will enable the recording of multiple modalities and analytes at a single location in the brain. An ideal multi-modal sensor would support a wide variety of measurements in a minimal volume, with no chemical or electrical crosstalk and without altering the local environment of the sensor, while allowing long- term, quantifiable, high spatial and temporal resolution, measurements of only the analytes/phenomena of interest. In practice, all measurement modalities are limited, but by combining multiple modalities in a single, configurable probe, researchers can leverage the strengths of the individual techniques to best suit the experiment at hand. The Brain-2025 Report (https://braininitiative.nih.gov/strategic-planning/brain-2025-report) states: “Our charge is to understand the circuits and patterns of neural activity that give rise to mental experience and behavior. To achieve this goal for any circuit requires an integrated view of its component cell types, their local and long‐range synaptic connections, their electrical and chemical activity over time, and the functional consequences of that activity at the levels of circuits, the brain, and behavior. Combining these elements is at present immensely difficult even for one circuit, yet we must also weave together the many interlocking circuits in a single brain. As the President said in his White House press conference, this is indeed a “grand challenge for the 21st century.” The proposed functionalized tetrode array, instrumentation, and support software will give researchers the experimental flexibility required to pursue these goals while ensuring experimental consistency (mechanical design), data quality (electronics design), experimental flexibility (software design), maximizing overall reproducibility while minimizing rodent use.