Understanding the rules of life

Category: Standard Studentships

Optical imaging of synaptic transmission: a transformative technology to probe the functional determinants of behaviour

Project No. 2338


Primary Supervisor

Prof Leon Lagnado – University of Sussex


Prof Vincent O’Connor – University of Southampton


3D live imaging is key to understanding biological processes such as nervous system control of behaviour, but it is challenging to achieve at speed.

One approach is selective plane illumination microscopy (SPIM) which uses a thin sheet of light imaged onto a high-speed camera: rapid z-movement of both light-sheet and imaging objective allows high-speed iobservation in 3D. We will develop a SPIM with improved resolution that uses two-photon Bessel beam excitation to image through the brain of a small live animal such as a larval zebrafish or C. elegans. This instrument, the first in the UK, will allow the student to develop a project based around visualizing the dynamics of signals transmitted at synaptic connections between neurons using the fluorescent glutamate reporter iGlUSnFR. This transformative technology will reveal how information flows through the brain as an animal interacts with its environment.

The student will explore these processes in two contexts: visually-driven behaviour in zebrafish and feeding behaviour in worms. In zebrafish, as in all vertebrates, excitatory synapses convey the visual signal through the retina to downstream circuits controlling behaviours such as prey-capture and the optomotor response. These behaviours are plastic and we will investigate how neuromodulators such as dopamine and serotonin act on synapses to adjust them. In the context of the worm C. elegans the project and its collaboration will investigate a second-to-second interaction between two distinct glutamate-dependent circuits that pivot feeding behaviour. The student will image the dynamics of this circuit as it controls feeding behaviour.

This project will suit a student interested in understanding the neural circuitry underlying behaviour and the establishment of a platform making use of an emerging transformative technology.