Karina Piotrowska1 , Annie Park1 , Scott Waddell1 1

Nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing properties of addictive substances. However, their heterogeneous composition makes it difficult to resolve how cell-type specific subunit combinations contribute towards addictive behaviour in vivo. Neonicotinoid insecticides are known nAChR agonists, and have been implicated in pollinator decline due to their addictive properties. We are studying these addictive behaviours in Drosophila, which permits an analysis of the roles of specific nAChR subunits within the dopaminergic system. Quantitative analysis of feeding revealed that flies form a robust dietary preference for sucrose laced with neonicotinoids. Moreover, chronic neonicotinoid exposure results in further elevated consumption of pesticide-laced sucrose, reflecting an experience-dependent adaptation in reward valuation. Optogenetic inhibition revealed an unexpected role for aversively reinforcing dopaminergic neurons in promoting neonicotinoid preference. Single-cell sequencing data of subtypes of dopaminergic neurons reveals differential cell-type specific expression of nAChR subunits. We are currently investigating whether this potential heterogeneity of nAChR composition drives functionally distinct cellular responses to neonicotinoids in vivo. Our studies will generate a cell-type resolved model of neonicotinoid function within dopaminergic circuits, which should uncover conserved neural mechanisms underlying neonicotinoid, and nicotine, addiction.

Centre for Neural Circuits and Behaviour, Department of Physiology, Anatomy and Genetics, University of Oxford