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

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 D 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 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 Hz to Hz high fill factor high resolution SLM To reduce cost and time to market MLO proposes to utilize an existing backplane representing a total savings of $ M and year of development Meadowlark will realize a prototype system within the Phase I and will utilize internal funds to complete the product Project Narrative Microscopy with spatial light modulators SLMs enables use of optical techniques to study neuronal circuit activity to both monitor and manipulate the activity of neuronal ensembles in vitro and in vivo As a result of successful worldwide research in this field suppliers of commercial two photon microscopes feel there is extensive product potential As such six major microscope suppliers have either licensed or are negotiating the patents to existing IP filed by Columbia University regarding use of photostimulation and adaptive optics in microscopy The Meadowlark Optics SLM as a key component in these commercial microscopes used to create the volume of foci for D scan less multi site programmable excitation Development of a high resolution high speed Hz to Hz SLM will provide commercial suppliers with a second generation microscope that matches the field of view that the SLM can excite to the field of view and resolution of commercial microscopes Additionally the SLM can be sold as a stand alone product addressing a wide range of markets