Development of neural networks & reactive oxygen species signalling in the nervous system
We are interested in understanding the rules and tools that nature uses to allow nervous systems to develop and coordinated function to emerge. As an experimental model, we work with the locomotor network of the Drosophila larva, which generates rhythmic crawling movements.
Drosophila has been extremely influential for our understanding of nervous systems, from neurogenesis to learning and memory. Drosophila brings many advantages: we can work with identified neurons to which we can return time and again; and target genetic manipulations to any nerve cell of choice, whose growth we can image and whose properties we can measure using electrophysiology.
In collaboration with Sean Sweeney at the University of York, we have been exploring how reactive oxygen species, a hallmark of ageing and neurodegenerative conditions, affect neuronal properties, growth and connectivity. We discovered a different face of reactive oxygen species, namely as metabolic signals that: i) inform neurons of their activity levels and ii) regulate adaptive adjustments via highly conserved redox sensors and downstream signalling pathways (Oswald et al., 2018). Moreover, when active, neurons generate reactive oxygen species also to inform neighbouring cells, as plasticity signals within the local community (Dhawan et al., 2021).
In collaboration with the Richard Baines lab, University of Manchester, we are investigating molecular, cellular and circuit mechanisms of critical periods of network development. It is during these late phases of nervous system development that nerve cell properties are specified, allowing network function to emerge. We are studying the signals that nerve cells/networks use to assess their status quo. We are investigating the mechanisms that initiate change during the critical period, and mechanisms that subsequently maintain the newly set cellular properties during later life.
- Oxidative stress - reactive oxygen species as novel plasticity signals in the nervous system
- Embryonic critical periods determine synaptic function and animal behaviour for later life
- Mechanisms of change – how critical period experiences specify and then maintain cellular properties
- Mechanisms of network adjustment during critical periods of nervous system development
- Modelling network adjustment during critical periods of nervous system development