Alexander Calhoun

BME PhD Proposal Presentation

Date: May 16, 2019

Time: 1:30 PM

Location: EBB 4029 (4th floor conference room)

Committee:

Robert Butera (Co-Advisor)

Hang Lu (Co-Advisor)

Gordon Berman

Patrick McGrath

Astrid Prinz

Philip Santangelo

Title: Adapting light sheet microscopy for functional imaging of the Caenorhabditis elegans nervous system

Abstract: As an animal navigates a complex environment, its nervous system must sort through a barrage of sensory inputs and use this information to implement behaviors that balance competing needs such as threat avoidance, feeding, and mate seeking. C. elegans is a particularly promising model organism for studying the mechanisms by which competing sensory inputs are processed. Its defined nervous system, optical transparency, and ease of genetic manipulation allow whole-brain imaging of intact, behaving animals, and microfluidics can be used to control the sensory environment with high precision.

Despite these advantages and available tools, whole-brain imaging of C. elegans is in its infancy. In practice, the technical requirements of optically sampling the full volume of the densely packed head ganglia with the resolution needed to segment and track individual neurons have tested the limits of existing imaging techniques. Light-sheet microscopy has proven effective for whole brain imaging in zebrafish and Drosophila larvae, but the specialized sample mounting makes it incompatible with microfluidics. We propose a light-sheet microscope design capable of whole-brain imaging of C. elegans in a microfluidic device. We will also demonstrate the utility of this imaging approach by investigating 1) local dendritic signaling of proprioception and 2) the influence of sex and internal feeding state on whole-brain activity, both of which present significant challenges for fluorescence microscopy.