Final Report Summary - EVONEURO (Evolution of olfactory circuits) Nervous systems have undergone remarkable diversification in their structure and function as animals have adapted to distinct ecological niches. What are the genetic mechanisms underlying neural circuit evolution? The project addressed this fundamental question in the Drosophila olfactory system, a superior "evo-neuro" model for several reasons: first, as in mammals, the Drosophila olfactory system has a modular organization, with individual olfactory receptors functionally and anatomically defining discrete sensory circuits that can be traced from the periphery to the brain; second, these circuits are dynamically evolving, with frequent acquisition (and loss) of receptors, olfactory neurons and odour-evoked behaviours with the ever-changing landscape of environmental volatiles; third, Drosophila offers unparalleled experimental accessibility to visualise and manipulate neural circuits; finally, a wealth of insect genomes permits comparative studies to relate intra- and interspecific genotypic and phenotypic variation. Through functional and anatomical comparisons of olfactory pathways for food-derived odours in ecologically-diverse drosophilid species, we have discovered profound alterations in the function and expression of specific olfactory receptors, as well as in the circuits in which they act. We have mapped the molecular determinants underlying the changes in receptor function, identified novel mechanisms that ensure their selective expression in sensory neuron populations, discovered molecules that may drive the evolution of novel neural pathways in the brain, and used cross-species genome-editing approaches to identify the causal basis of the adaptations of circuit properties as well as the relevance of these for species-specific odour-guided behaviours. By addressing how particular olfactory circuits and behaviours have evolved in Drosophila, the project has provided general insights into the genetic mechanisms of nervous system evolution relevant both for other brain regions and for other species. Determining how brains have been sculpted through random mutation and natural selection in the past may enable future directed manipulation of the connectivity and activity of neural circuits, to enhance our understanding of brains and our ability to repair them.
