Miniature, integrated and mass-producible fluorescence microscopes for in vivo brain imaging in freely behaving rodents - Project Summary
There is increasing awareness that aberrant neural circuit activity is a core manifestation of many
neuropsychiatric diseases, including autism, schizophrenia, depression and Alzheimer's disease. This
realization has opened tantalizing prospects for more powerful and precise therapeutic approaches based on
retuning of abnormal circuit activity. However, we still lack crucial understanding of neural activity patterns
during normal behavior and how these patterns are altered in disease. Many rodent models of human brain
diseases are now available, but neuroscientists are still hindered by lack of a technology for visualizing activity
in large populations of genetically identified neurons in the brains of behaving animal subjects. Inscopix, Inc.
spun out of Stanford University to commercialize a miniature fluorescence microscope technology that lets
neuroscientists visualize Ca2+ dynamics in up to 1200 neurons simultaneously in awake, behaving rodents at
cellular resolution. The microscope is easily carried on the head of a mouse or rat, and enables continuous
recording from the same group of neurons in a single animal for periods of days to weeks. Used in conjunction
with genetically encoded Ca2+ indicators and our custom-designed optical microendoscope probes, the
microscope enables targeting of predefined neuronal subpopulations, and entry to brain regions inaccessible to
other large-scale recording technologies. In Phase I, we developed and validated a new version of the
microscope that is substantially higher performing and more robust than the original Stanford prototype.
Around it we built the nVista imaging system: an end-to-end solution for in vivo brain imaging that includes
the miniature microscope with an integrated HD camera and electronics, and user-friendly data acquisition
hardware and software. The nVista system has now been disseminated for beta testing to over 100 labs around
the globe. This Phase II project will move the nVista system forward in its next steps towards marketing to the
general neuroscience community, through the following aims. (1) Create a next-generation version of the
nVista system for commercial dissemination. Making use of feedback from early adopters, we will refine the
system's design for greater performance, reliability and ease of use, by incorporating an electronic focusing
mechanism, enabling higher speed data acquisition and seamless interfacing with other data collection
systems; (2) Extend the technology to rats by developing an accessory array for the nVista microscope that
includes a new base plate attachment mechanism, protective head-mounted cone and cable sheathing, optical
probes, and an optical data link to support commutators; and (3) Develop a next-generation data analysis
platform with faster processing, customizability, and better visualization tools.
