Nervous system reprogramming by flexible neuropeptidergic networks
Animal brains are wired according to a series of remarkable genetic programs that have evolved over millions of years. Much of our behavior, however, is the product of experiences that happen to us on much shorter time scales. The ability of the nervous system to properly respond to aversive stimuli is crucial for animal well-being and survival. In many vertebrate sensory systems, persistent stimuli are coded by tonically active neural circuits. As opposed to phasic sensors that adapt rapidly, tonic neurons reliably convey stimulus intensity over long time periods and are essential for cues that need to hold attention, e.g. harmful stimuli. How persistent aversive stimuli are molecularly encoded and reprogram behavior remains elusive. Our working hypothesis is that aversive challenge recruits a network of neuropeptide signaling pathways that is sculpted by experience and mediates diverse acute and long-lasting behavioral responses. 

We will test this hypothesis on the small and well-described oxygen-sensing circuit of C. elegans. Because neuropeptidergic networks are notoriously complex, such a highly controlled context for pioneering research on their involvement in tonic aversive signaling is preferable. First, my team will develop tools for the in vivo reporting of neuropeptide GPCR activation, establishing SPARK in a living animal, which will allow conceptual advancements with unprecedented detail. Pertinent questions we will then address include: ‘How do cellular networks respond to changes in neuropeptidergic network activities in an aversive signaling context?’; ‘What are behavioral implications of neuropeptidergic network activity upon aversive challenge?'; and ‘Do neuropeptidergic networks contribute to cross-modality?'

We expect that on the long term, this project will impact our understanding of how tonic peptidergic circuits influence and organize habituation, learning, forgetting and modus operandi of nervous systems in general.