The connectome of olfactory memory circuits in the adult fly (360G-Wellcome-203261_Z_16_Z)

Connectomics, establishing comprehensive neuronal wiring diagrams at the resolution of single synaptic connections, is still in its infancy. Although most neuroscientists are confident that connectomics will eventually have a major impact, doubts remain about when this will happen. We propose a project that within 4 years could transform an important field of neuroscience – the circuit basis of learning and memory – by reconstructing the olfactory memory circuits of Drosophila. A consortium of laboratories at HHMI Janelia has generated a complete serial section transmission EM volume of an adult female Drosophila brain. This 106 TB volume (100x larger than any previously imaged whole brain) will have a major impact on over 200 laboratories working in Drosophila neurobiology. We will reconstruct input and output neurons of the primary associative learning centre, the mushroom body, along with selected upstream layers bringing teaching signals and downstream layers mediating descending control of behaviour. This will reveal the complete network and synaptic organisation of a memory centre, whose logical principles, including sparse coding, dopamine-dependent plasticity, valence segregated by neuronal population, and network recurrence, are all relevant to mammalian brains. This will enable a wealth of experimental circuit studies as well as piloting large-scale, geographically-distributed connectomics.