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Mechanisms for developing stable networks

Supervisor: Dr Matthias Landgraf

Project summary:

Neural networks form as a multitude of cells form synaptic connections with one another. How the inherent variability of each and every one of these constituent parts can be overcome and lead to the emergence of a stable network with a robust output, remains unresolved.  This very phase of network formation is known to be associated with heightened plasticity and is called a ‘critical period’.  

Ultimately, this needs to be understood at the network level. With the discovery of a well defined critical period the motor system of the fruitfly, Drosophila melanogaster, this can now be achieved, thanks to recent connectomics advances. Building on these we will study how network function emerges and how stability is achieved, by having access to identified connected nerve cells and the network as a whole.

Using functional imaging, we will chart the emergence of coordinated network activity. We are establishing how patterns of connectivity develop; and how there are impacted by critical period perturbations, using novel genetic reporters for synapses and super-resolution imaging methods. Modelling will be used in collaboration with Dr. Timothy O’Leary (Dept. of Engineering) to identify adjustment rules and the different underlying circuit motifs.

What the student will be doing:

In this project you will use a combination of genetics, imaging and electrophysiology to characterise the developmental events around the critical period. Behavioural assays include larval crawling and electroshock. A combination of semi-intact preparations (for pharmacological manipulations) or intact animals (manipulated using thermo- and opto-genetics) will be used to study changes in neuronal structure and function (using functional imaging and electrophysiology). Super-resolution imaging methods, such as expansion microscopy and ‘GRASP’ will allow quantitative imaging of synapses.

References:

1.     Oswald MCW, Brooks PS, Zwart MF, Mukherjee A, West RJH, Giachello, CNG, Morarach K, Baines RA, Sweeney ST and Landgraf M. (2018). Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity.  eLife, 7. http://doi.org/10.7554/eLife.39393

2.     Giachello, C. N. G. and Baines, R. A. (2015). Inappropriate Neural Activity during a Sensitive Period in Embryogenesis Results in Persistent Seizure-like Behavior. Curr Biol 25, 2964–2968.

3.     Zwart, M. F. et al. Selective Inhibition Mediates the Sequential Recruitment of Motor Pools. Neuron (2016). doi:10.1016/j.neuron.2016.06.031

4.    Couton L., Mauss A.S., Yunusov T., Diegelmann S., Evers JF., Landgraf M. Development of connectivity in a motoneuronal network in Drosophila larvae. Curr Biol. 25:568-76 (2015).  doi: 10.1016/j.cub.2014.12.056.

5.  Schneider-Mizell, C. M. et al. Quantitative neuroanatomy for connectomics in Drosophila. Elife 5, (2016).