Modulation of circuit dynamics by noradrenergic signalling in the annelid model Platynereis

In nervous systems, a large number of neuromodulators regulates the activity of every neural circuit. The monoamine noradrenalin (norepinephrine) is a major neuromodulatory transmitter that promotes wakefulness and arousal and regulates autonomic functions. Until recently, noradrenalin signalling was considered to be specific to vertebrates. Our discovery of functional noradrenalin signalling in marine invertebrates has overturned this long-held view. In this project, we propose to investigate noradrenergic signalling in the larval stages of the marine annelid Platynereis dumerilii, a laboratory animal and powerful new model for connectomics and circuit function. We will take advantage of the Platynereis system to obtain novel cellular-level insights into noradrenergic signalling through a systems-neuroscience approach. To analyse the functions of noradrenalin and its regulators at single-cell resolution, we will generate transgenic constructs and CRISPR-induced knockout lines and analyse wild-type, knockout and transgenic larvae with whole-brain activity imaging and various behavioural paradigms. We will establish whole-body wiring diagrams through serial EM reconstruction and map the components of noradrenergic signalling to the connectome. The use of this simple and accessible invertebrate genetic model will thus allow us to study noradrenergic signalling in unprecedented detail in a fully-mapped nervous system.