Project Summary/Abstract:
To understand the function and dynamics of neural circuits that control behaviors and cognitions, we need to observe the neuronal network at a cellular resolution over large spatial scales across multiple brain regions. Although two-photon fluorescence microscopy (TPM) combined with genetically encoded function indicators has provided a paradigm shift in neuroscience by enabling cellular resolution functional imaging deep in brain tissue, current TPM technologies still fall short of achieving whole-neocortex coverage. In this project, the engineering team at Purdue and the neuroscience team at UCSD will join the force to develop the Light Pipe Microscope (LPM) and enable ultra-large-scale whole-neocortex calcium imaging. Compared to conventional TPMs, LPM offers three advantages. First, LPM offers unparalleled signal collection capabilities over a large imaging field of view, which translates to superior imaging quality, depth, and extremely low photobleaching for long-duration continuous recording. Second, LPM features an extremely compact body, which allows multiple LPMs to be densely or sparsely packed to simultaneously image the curved brain surface. Third, LPM can be constructed with low-cost components and is fully compatible with common lasers, scanners, data acquisition systems, and software, which will facilitate broad dissemination. In particular, the single LPM and the dual LPMs can be constructed as add-on components to the existing two-photon imaging systems with a small fraction of the cost of a commercial TPM. They will convert the existing two-photon systems for ultra-large-scale cellular resolution functional imaging of mammalian brains. Through the proposed development, we will have the fully developed and thoroughly validated LPM, each with a large FOV and unparalleled signal collection efficiency. A low-cost ($4,800) single unit (as an add-on) can convert the widely used two-photon scopes into mesoscopes with unmatched signal levels. The utilization of two or more LPMs will provide unprecedented ultra-large-scale two-photon imaging coverage, which will transform the study and understanding of mammalian brains.
