Head-mounted miniature microscopes for combined calcium imaging and electrophysiological measurement of neural circuit function in deep brain regions of behaving macaques - PROJECT SUMMARY
A consensus has emerged in the Neurosciences over the last decade regarding the critical importance of
understanding brain function at the level of neural circuits. Such an understanding can help us bridge across
scales of investigation to provide a more comprehensive model of brain function, while also providing a more
direct link to the dysfunctions associated with neurological disease. Inscopix, through its flagship product,
nVista, in part facilitated by previously awarded NIH/NIMH Brain Initiative SBIR grants, is now providing
neuroscientists in over 300 labs worldwide with the ability to monitor cellular-resolution, large-scale calcium
dynamics in freely behaving rodents, leading to breakthrough research on the neural circuit mechanisms
underlying basic behaviors. Nevertheless, to advance our understanding of higher-cognitive function, complex
behavior and mental health, a critical need remains to translate such capabilities to research using non-human
primates (NHPs), a model with a behavioral repertoire and brain structure similar to that of humans.
In this Fast-Track proposal, we will build on our prior successful SBIRs and the success of nVista for rodents,
and develop and commercialize a first-of-its-kind platform for NHP neural circuits research, enabling large-
scale optical and electrophysiological (ephys) recordings deep and distributed in the brain and, critically, doing
so with a streamlined surgical workflow and plug-n-play operation to aid mass adoption in labs across the
world, creating new capabilities for studying human-relevant cognition, behavior and mental disorder. In Phase
1 we will design and fabricate prototypes of new probes and implant hardware, which will include virus-coated
lenses, integrated baseplates and a cranial chamber system for a streamlined surgical workflow (Aim 1),
together with longer lenses for deeper brain imaging, electrode-integrated lenses for same-site imaging and
ephys, and a new baseplate supporting longitudinal tracking of neurons (Aim 2). We, along with two beta lab
partners, will validate performance of these prototypes in NHPs (Aim 3). In Phase 2, we will design and
fabricate a fully integrated hardware and software NHP platform for multi-system, simultaneous imaging and
ephys (Aim 4) and fabricate 15 complete, user-friendly systems, incorporating feedback from Phase 1 and
enhancing key features to enable a larger set of scientific use cases (Aim 5). We will perform extensive in vivo
experiments with a larger set of beta sites to demonstrate the scientific value of all features (Aim 6). At the end
of Phase 2, we will have a new platform for streamlined, fully integrated calcium imaging and ephys in deep
brain regions of behaving NHPs. This platform will be the first-of-its-kind for neural circuits research in NHPs,
fully designed and validated to meet the unique needs of the NHP neuroscience research community. This will
allow them to ask new questions about the neural circuit mechanisms underlying perception, higher-cognitive
function and complex behavior, as well as the neural circuit abnormalities underlying neurodegenerative and
neuropsychiatric disease, which together will greatly advance our understanding of human mental health.
