Wide field of view 3D microscopy for calcium imaging and photostimulation

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Project Summary/Abstract Mental disease, including schizophrenia, depression and autism spectrum disorders, are still poorly understood, although it is clear that they mostly represent cortical disorders. The cortex is the primary site of higher mental functions, and despite extensive research, there is still no unified theory of how the cortex works. This is partly due to the fact that neuroscientists have traditionally relied on microelectrodes to record the activity of individual cells. However, cortical circuits are composed of millions of neurons and it is conceivable that single cell measurements alone will not be sufficient to unravel function of the brain. Optical imaging techniques tackle this emergent level of neuronal circuit activity and enable to image the activity of neuronal ensembles, in vitro and in vivo, while preserving single cell resolution, something that brain imaging techniques such as MRI or PET, cannot do. Moreover, the development of genetically encoded photosensitive proteins (optogenetics) and optochemical (caged) compounds offers the opportunity to not only image the activity of many neurons but also to optically control them. Advances in optogenetics has led to the development of two-photon microscopes combined with spatial light modulators (SLM), that allow the customer to split the laser beam into a holographic pattern that can be used to image activity or photoactivate neurons simultaneously in 3D. Multiple commercially available microscopes are now offered. Additionally researchers are customizing their own microscopes as a low cost alternative to purchasing new commercially available microscopes. The Meadowlark Optics (MLO) SLM is preferentially utilized due to the unprecedented response time a factor of 8 faster than competing SLMs, enabling more complex studies of brain function. However, the limited resolution of the SLM leads to studies over a smaller volume, and low fill factor leads to optical losses. To address these concerns MLO is proposing the development of a high speed (142 Hz to 500 Hz), high fill factor (95%), high resolution SLM. To reduce cost, and time to market MLO proposes to utilize an existing backplane, representing a total savings of $1M, and 1 year of development. Meadowlark will realize a prototype system within the Phase I, and will utilize internal funds to complete the product.