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A critical period shapes motor network development & function

A critical period shapes motor network development & function 

Supervisor: Dr Matthias Landgraf

 

Project summary:

As neural networks assemble and function emerges, they usually pass through a period of tuning during which they display exceptional plasticity – often referred to as ‘critical periods’. Homeostatic mechanisms are critical to network tuning. Importantly, the homeostatic set point of the network seems to be determined during the critical period, and when the network excitation/inhibition balance is disturbed during this period, it leads to the formation of an unstable network prone to seizures. 

How these periods of high plasticity are developmental regulated and genetically specified remains incompletely understood. Even less is known about how the network set point is determined during the critical period and maintained thereafter. Together with our collaborators in the Richard Baines lab in Manchester and the Jan Felix Evers lab in Heidelberg, we are studying these questions, using as a model system the locomotor network of the Drosophila embryo and larva.

Specifically, we are asking whether the timing of the critical period is developmentally hard-wired or regulated by neuronal activity or neuron-glia interactions?  And how do neuronal connections develop differently when network activity has been disturbed during the critical period leading to an abnormal homeostatic set point?  Based on our work on homeostatic structural plasticity, which highlighted Reactive Oxygen Species and PKA as key signalling pathways, we will use genetics to study the roles of these and other candidate pathways in network tuning during the critical period.

 

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. 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, allow quantitative imaging of synapses.

 

References:

1.     Oswald MCW, Brooks PS, Zwart MF, Mukherjee A, West RJH, Morarach K, Sweeney ST and Landgraf M. (2016). Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity.  bioRxiv 081968. 

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.     Milton, V. J. et al. Oxidative stress induces overgrowth of the Drosophila neuromuscular junction. Proc Natl Acad Sci U S A 108, 17521–17526 (2011).

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.     Tripodi, M., Evers, J. F., Mauss, A., Bate, M. & Landgraf, M. Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input. PLoS Biol 6, e260 (2008).