A Bidirectional Neural Probe for Optical, Electrical and Chemical Probing of Neural Dynamics

Within the brain, billions of neurons communicate via diverse electrical and chemical signaling mechanisms. To begin to unravel how the function of specific neuronal subtypes within neural circuits gives rise to behavior, methods of recording and modulating neural activity across electrical, optical, and chemical modalities have been developed. Each technique has its own set of advantages and constraints, especially regarding spatial and temporal resolution, cell-type specificity, and the necessity of genetic manipulation. Combining multiple neural interfacing modalities into a single probe can leverage their unique advantages to reveal new insights into neural circuit dynamics. Here, we report a bidirectional, multifunctional neural probe that, for the first time, combines six modalities of neural interfacing: electrophysiology, electrical stimulation, fiber photometry, optogenetic stimulation, fast-scanning cyclic voltammetry (FSCV), and drug/gene delivery. We employed convergence thermal drawing to fabricate meters-long 300 µm diameter flexible fibers containing a polymer optical waveguide for fiber photometry and optogenetics, a microfluidic channel for drug/gene delivery, and carbon nanotube (CNT) electrodes for electrophysiology, electrical stimulation, and FSCV recording of a neurotransmitter dopamine (DA). Polymeric components with similar glass transition temperatures (T_g) were first machined into a macroscale preform containing the optical waveguide, a microfluidic channel, and hollow channels for CNT yarn electrodes. During the draw, the polymer preform was heated above its T_g and stretched such that the hollow channels shrank and converged around high T_g CNT yarns, which were thus integrated into the microscale fiber. This resulted in a multimaterial microscale fiber with conserved cross-sectional geometry compared to the preform. We demonstrate the use of our multimodal neural probe<i> in vivo </i>by implanting probes into the ventral tegmental area (VTA) and nucleus accumbens (NAc) of adult mice and investigating mesolimbic dopaminergic reward pathways. During implantation, the embedded microfluidic channel was used to deliver opsins (ChrimsonR) and optical reporters (dLight1.1) to the target brain regions. Following recovery, we performed combinations of electrical and optical stimulation, coupled with fiber photometry, electrophysiology, and FSCV recording to illustrate the utility of our multimodal probe for studying circuit level neural dynamics.