Leaflabs, LLC — Department of Health and Human Services SBIR Phase I: 101

Description

DESCRIPTION provided by applicant Recording all the neural activity in a D volume with millisecond timescale precision is a key goal of the BRAIN initiative Recently in a collaborative project with the Vaziri lab IMP Vienna we adapted the strategy of lightfield microscopy for D volumetric imaging of fluorescent neural calcium responses Prevedel This technology enables computational reconstruction of a D volume from an image by simultaneously capturing the angle of incident light rays in addition to their intensity Imaging can occur as quickly as the fluorescent neural activity reporter allows Chen we imaged the entire larval zebrafish brain at Hz However the spatial resolution for lightfield microscopy is poo resulting in low signal to noise ratio SNR as well as difficulty in automatically segmenting neural anatomy which is key to linking neural activity to underlying circuitry This spatial resolution limit is a fundamental issue with lightfield microscopy since to gain D imaging capability one must sacrifice spatial resolution there are only so many pixels on the camera Accordingly we here propose to perform the first whole brain recording of a larval zebrafish with single neuron resolution by increasing the total pixel count of our existing system by an order of magnitude whilst improving the SNR by leveraging a six fold increase in frame rate Our existing lightfield imaging system Prevedel and others Levoy Cohen use an array of microlenses to effect the trade off of spatial for axial resolution An alternativ approach captures the lightfield using an array of cameras without any microlenses Our novel design combines both approaches at an unprecedented scale Our scalable data acquisition system Willow see preliminary data combined with cameras designed in house limit the cost of our system to of a traditional two photon microscope In this way we aim to develop a user friendly system capable of imaging all of the neurons in a D volume at speeds comparable to the natural timescales of neural activity whilst keeping an eye towards polishing our system for marketability and widespread use PUBLIC HEALTH RELEVANCE Lightfield microscopy systems allow direct observation of neural activity in animal subjects over large D volumes of tissue This facilitates the study of crucial neuroscientific topics such as development learning and memory and cognition as well as brain diseases such as Alzheimerandapos s epilepsy Parkinsonandapos s and depression Currently these systems are custom engineered luxury items for research laboratories and have limited field of view but LeafLabs plans to commoditize them by developing new cheaper and higher density cameras and data acquisition systems and polishing this technology into a system made commercially available off the shelf