###Engineering a hybrid microscopy platform for brain-wide, multi-modal mapping of neuronal features in larval zebrafish
Project ID: 2228bd1183 (You will need this ID for your application)
Research Theme: Engineering
UCL Lead department: Division of Biosciences
Lead Supervisor: Steve Wilson
Project Summary:
Mapping information flow in multicellular systems for comprehensive understanding of tissue development and function is a major challenge in biology. This is epitomised in the brain where neuronal activity dynamics over different time scales impact brain development, function and behaviour. Anatomically distributed, temporally complex activity patterns are not a mere consequence of shared connectivity between neurons but also depend on their underlying genetic composition. The differential expression of genes determines, for instance, which set of neurotransmitters and neuropeptides are released and which set of receptors are expressed by each neuron to facilitate and modulate synaptic communication. It is therefore imperative to classify spatially distributed cell types in the brain through a feature rich description of multi-modal neural attributes.
This project will establish a novel optical and microfluidic platform to acquire multi-dimensional, multi-modal datasets characterizing neural cells across the larval zebrafish brain, both by functional and molecular signatures. A multi-view, hybrid light-field and light-sheet microscopy system for isotropic resolution, brain-wide molecular profiling of neuronal dynamics will be developed. Light field microscopy will enable very rapid volumetric acquisition of neuronal dynamics as it can capture in 2D spatial and angular content of the emitted fluorescence, which allows reconstruction of the imaged 3D volume through angular information. The spatial resolution of the functionally imaged volume will be enhanced through deconvolution driven by deep learning. Subsequently, the expression patterns of multiple RNA molecules encoding for neurochemicals will be mapped through the multi-channel, dual view, light-sheet microscopy mode. The staining and mapping of RNA expression patterns will be delivered through a newly developed microfluidic Hybridization Chain Reaction (HCR) system.
This novel platform will enable multi-modal mapping of neuronal classes facilitating a deeper understanding of how molecularly diverse cell types participate in brain function and behaviour.