The IF-GF project aims to decipher in vivo the neurobiology of sensory disturbances induced by ciguatoxins (CTXs), which cause ciguatera fish poisoning and have recently become a European food safety concern as emerging toxins. CTXs are the most potent known activators of voltage-gated sodium channels, without isoform specificity. The strong predominance of specific sensory disturbances in ciguatera suggests that CTXs activate specific subsets of primary and/or dorsal horn somatosensory neurons, which is consistent with the population coding theory. The first specific objective is to characterize the molecular markers of primary and superficial dorsal horn (SDH) sensory neurons responding to CTXs and the molecular players involved in the CTX-induced spontaneous itch and cold allodynia. Next, the planned action aims to examine the role of sensitization of sensory receptors and channels in the sensations evoked, and to identify the mediators and mechanisms involved. To achieve this, the methods used will combine a behavioural test capable of distinguishing between scratching and pain behaviours, functional methods including in vivo electrophysiological recordings in SDH neurons and calcium imaging in primary neurons, and a variety of tools comprising neurotoxic ablation, genetic invalidation, and chemogenetic inhibition of specific neuronal subpopulations. These approaches, still used by a few teams around the world to explore neural circuits, are an outstanding opportunity to advance research on sensory disorders induced by CTXs. In addition, using CTXs as singular tools, the action has the potential to uniquely complement research on itch and pain neurobiology. The fellow will benefit from the world-renowned expertise and experience of the partner laboratory (at UC Davis, USA) to acquire new technical skills and knowledge essential for her future career, and from its international network to broaden her prospects for research collaboration.
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