Motor network connectivity – wiring motifs and function
Supervisor: Dr Matthias Landgraf
Motor networks, i.e. parts of the central nervous system that generate behaviour, are much less well understood than many sensory systems. One reason has been their distributed nature. Recently, a large scale connectomics approach, centred around dense reconstructions of neuronal networks from a serial section Transmission Electron Microscopy (ssTEM) volume of Drosophila larval brain, has begun to yield exciting new insights. We thus discovered the neural basis for the generation of sequential intrasegmental muscle contractions, which are characteristic of larval crawling and also akin to motor motifs of vertebrate limb movements. Intriguingly, functional imaging suggests most body wall muscles receive near co-incident excitation, and that differences in contraction phases are implemented by selective feed-forward inhibition.
This now begs the question as to how such feed-forward inhibition is regulated to bring about coordinated phase shifts between major muscle groups. Moving deeper into the network, what are the circuitry and wiring motifs that integrate sensory feedback? And how are more intricate movement patterns choreographed that might call upon the great diversity of larval muscles (30 muscles in each half segment)?
What the student will be doing:
This project can be very versatile. The starting point will be computer aided 3D reconstructions of neurons from an existing ssTEM volume to gain new insights into the upstream motor circuitry. Genetics, using new genetic expression lines, optogenetic manipulations, functional imaging and electrophysiological recording are all techniques appropriate for further exploration. To image synaptic connections we use GRASP and aim for introducing expansion microscopy.
1. Zwart, M. F. et al. Selective Inhibition Mediates the Sequential Recruitment of Motor Pools. Neuron (2016). doi:10.1016/j.neuron.2016.06.031
2. Couton, L. et al. Development of connectivity in a motoneuronal network in Drosophila larvae. Curr Biol 25, 568–576 (2015).
3. Schneider-Mizell, C. M. et al. Quantitative neuroanatomy for connectomics in Drosophila. Elife 5, (2016).
4. Chen, F., Tillberg, P. W. & Boyden, E. S. Optical imaging. Expansion microscopy. Science 347, 543–548 (2015).
5. Feinberg, E. H. et al. GFP Reconstitution Across Synaptic Partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron 57, 353–363 (2008).