Regulation of synapse growth and neuronal homeostatic adjustment by Reactive Oxygen Species, metabolic by-products of mitochondrial respiration. As neural networks form, synaptic connections between nerve cells need to be tuned, so as to be able to generate appropriate network output. Such plasticity it central to nervous system formation, function (e.g. for learning) and maintenance. At the level of single nerve cells, we have documented both physiological and structural adjustments. At the level of entire networks, for instance in the case of locomotor networks, one can see how embryos progressively refine their movements prior to hatching/birth. Though a fundamental property of nervous systems, we still understand relatively little about how nerve cells ‘know’ how to adjust. In collaboration with the Sweeney lab at York we discovered a probably ancient signaling pathway: nerve cells use a by-product of mitochondrial ATP metabolism, namely reactive oxygen species (ROS), as secondary messengers to inform about activity levels (proportional to ATP consumption). The importance of ROS is underlined by their accumulation with ageing and neurodegenerative conditions, associated with cognitive defects. We work with the Drosophila motor system, which allows us to work with identified connecting cells that can be genetically manipulated with unprecedented precision. We use confocal imaging, electrophysiology and computer aided 3D morphometry. This work links in with other projects in the lab, which investigate the logic of motor network development: how networks emerge from neural progenitor/stem cells, patterning of synaptic connections (in part using TEM serial reconstructions) and regulating the plasticity of dendritic growth.
- 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).
- Zwart, M. F., Randlett, O., Evers, J. F. & Landgraf, M. Dendritic growth gated by a steroid hormone receptor underlies increases in activity in the developing Drosophila locomotor system. Proc Natl Acad Sci U S A (2013). doi:10.1073/pnas.1311711110
- 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).