NCS-FO:Collab:Multimodal sampling of neural ensembles: A high-density opto-electro-chemical neural interface for simultaneous electrical recording and optical imaging of cell-types

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This project develops novel devices and methods to record the electrical activity of large numbers of neurons while simultaneously identifying their specific cell types. Specific cell types have precise computational roles in neural information processing systems, but in most cases cell types are not identifiable from electrical activity alone. In cortical regions responsible for decision making, the difficulties posed by intermingled cell types are further complicated by layers, recurrent connections, and the multitude of interneuron types. In order to understand how neural information processing systems mediate decision making, it is necessary to (1) record simultaneously from many neurons to quantify high-dimensional activity, (2) identify and ascertain the precise computational roles of the cell types within those ensembles, and (3) chemically perturb neural ensembles to determine causal functionality. This project will for the first time enable all 3 of these capabilities simultaneously. The proposed neural interface will incorporate recording electrodes, neurochemical stimulators, and flat optical imager waveguides all in the slim form factor of an implantable micro-needle. This device will be used to study the detailed circuit-level functionality of specific cell types involved in the population activity of neurons. The collaboration between a team of engineers and biologists provides a unique interdisciplinary environment for training graduate and undergraduate students working on this project. The PIs will also design a new course on neurotechnology to teach students about the needs in neuroscience research and opportunities in engineering to design next generation neural interfaces. This project incorporates an integrative approach based on innovations in technology (nanotechnology, photonics, and neurotechnology) as well as advancements in fundamental neurobiology and transcriptional profiling of cells based on optical tagging to shed light on the role of specific cell types on collective actions of neurons during behavior. Building on a recently developed polymer-based optical waveguide platform with embedded micromirror ports, the investigators will design a novel flat imager that can be monolithically integrated with micro-electrodes to optically image the cell identities, while simultaneously recording their electrophysiology activity. The proposed neural interface (i) is compact and flexible, (ii) combines high-density electrical recording with chemical stimulation, (iii) contains electrically actuated nanocomposite polymers, and (iv) enables on-shank fluorescent imaging using a novel micro-imager array based on parylene polymer photonic waveguides. The utility of this technology platform will be demonstrated for studying cell types involved in encoding sensory sensations in rats during whisker stimulation. The developed multimodal probes will also be disseminated to different neurobiology labs to be used in other experimental contexts to amplify the impact of the proposed project. The outcome of this cross-field research will be (i) a new technology platform that can be used to test various neuroscience hypotheses on the role of specific cell types in encoding and transforming information in brain and (ii) a valuable dataset that can enhance existing mathematical models of neuronal population activity by adding new dimensions to the existing large-scale data based solely on electrophysiology, and will enable an entirely new class of neurobiology experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.