Development of compressed ultrafast microscopy for real-time multi-scale neuroimaging

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A prevalent goal in neuroscience is to record fast, spontaneous neural activities occurring at varied spatial and temporal scales in real time. Conventional electrophysiology relied on microelectrodes to record neuron's membrane potentials. However, in general, this invasive approach is limited in the number of recording sites, vulnerable to environmental electrical noises, and challenged for longitudinal monitoring. Optical recording, on the other hand, has emerged as an attractive approach to measuring neural activities with inherent advantages in non-invasiveness, recording parallelism, and spatiotemporal scalability. Optical voltage imaging encompasses two major constituents: voltage indicators and optical imaging instruments. Recent advances in biochemistry have enabled fast-response, high-sensitivity fluorescent voltage indicators. However, existing optical instruments still lack sufficient speed, scalability, and sensitivity. Thus, real-time, multi-scale optical imaging of neural activities has not been achieved.******The overall objective of this Discovery program is to develop unique imaging techniques and devices for real-time, multi-scale optical neuroimaging. Our long-term goal is to map the functional connectome of the brain. For the next five years, we propose three projects to investigate optical voltage imaging from the technological development and neuroscience applications in a collaborative effort. Specifically, these projects aim ***(1) To develop compressed ultrafast microscope (CUMIC) for real-time, multi-scale optical voltage imaging***(2) To investigate biophysical properties of the axon initial segment and the node of Ranvier under pathological conditions in vitro using CUMIC at 10 kHz–2 MHz ***(3) To determine neural encoding and neuroplasticity to sensory stimulations in freely behaving animals using CUMIC at 1–10 kHz ******The results of the proposed program will represent a unique contribution in biophotonics by significantly enhancing our imaging capability of neurons from sub-cellular to organism levels. The state-of-the-art CUMIC system will greatly assist neuroscientists in understanding open questions in neuronal biophysics, circuit neuroscience, and behavioral outputs. CUMIC will also pave the way for real-time high-spatiotemporal-resolution neuroimaging in the brain cortex in the future. In addition, the advanced imaging technique developed in this program will find a diverse range of applications, including nanotechnology and molecular biology. Finally, this program will train 3 Ph.D., 1 M.Sc., and 10 summer students. Gaining valuable expertise ranging from optical engineering to neuroscience applications, these highly qualified personnel will contribute their knowledge in areas of photonics, medical physics, and biochemistry that are critical for Canada's future success in the global knowledge-based economy.