This project directly addresses a technology need recognized by the solicitation: “Novel instrumentation that improves current technologies to determine circuit connectivity and neural activity.” It does so by creating a neurotechnology hub, called Nemonic (NExt generation MultiphOton NeuroImaging Consortium). This hub will develop, disseminate, and advance multiphoton neuroimaging technologies “for investigators studying brain structure and function in diverse species.”

The moment-to-moment dynamics of neuronal activity during coding and behavior is distributed across multiple brain areas. Thus, to reverse engineer the connectivity and operating principles of neural circuitry, scientists must measure activity with individual neuron resolution in multiple brain areas simultaneously. Multiphoton (usually two-photon) imaging of calcium indicators enables dense and chronic sampling of neural activity with individual neuron resolution. However, currently available commercial imaging systems for this approach can only resolve neurons in a single brain area at a time. Therefore, new technology must be developed. Emerging technology, developed in part through a prior NSF BRAIN EAGER grant (Smith), enables optical recordings of 10e4 – 10e6 neurons distributed across > 10 cortical areas without moving the microscope or the animal.

Key Research Resources Being Developed and Disseminated

The Nemonic project has three parts. First, there is a development component, called DEV, to create new technology to overcome critical barrier to progress in neuroscience. In a series of Case Studies, neuroengineers will develop custom instrumentation to enable currently impossible neuroscience experiments. A proven work flow involving custom optics and iterative refinement, and culminating in commercially produced parts, will be used to create the custom instrumentation. The Case Studies involve a range of animal models (mice, ferrets, cats, and monkeys), and optical and instrumental challenges.

Second, there is a dissemination component, called DISSEM, to spread this technology broadly to other labs. All engineering materials and resources generated in the Case Studies will be open-sourced and released to the broader public in thoroughly documented and curated web resource. Components and systems developed in the Case Studies will be made commercially available. Also, a series of workshops will be held to train scientists on how to design and build custom systems for multiphoton neuroimaging.

Third, there is an advancement component, called ADV, to push the technology of multiphoton neuroimaging into the next frontier. Two technologies will be pursued: miniaturized, highly integrated photonic systems for practical and scalable head-mounted multiphoton neuroimaging in freely moving animals; and superresolution imaging to resolve structures relevant to synaptic and molecular dynamics in vivo. Also, a series of meetings will be held to promote novel collaborations and more rapidly advance technologies that are relevant to multiphoton neuroimaging in the future.

Reaching Out to the Community

The Nemonic project will work towards full participation in STEM fields through outreach efforts from K-12, research experiences for high school students and URM in graduate school, and providing fellowships to URM to attend meetings and workshops that are part of the project. The project will also prioritize partnerships with minority-owned businesses. STEM education will be enhanced through state-of-the-art workshops, and online resources created during the project. Partnerships between industry and academia will be increased through interactions and consultations with industry leaders, and these will include interactions with trainees working on the project. Innovative technology developed in this project is relevant outside of neuroengineering, to fields real-time imaging feedback during manufacturing, widely tunable integrated photonics, and 3D printing.