SCCMMI SIGNED

Project "SCCMMI" data sheet

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 Project objective

Directed behavior emerges from neural integration of sensory stimuli, memory of prior experience and internal states. We seek an understanding of these conserved neural mechanisms using genetically-encoded tools and the relatively small brain of the fruit fly Drosophila. By temporally controlling neural function memories can be implanted and internal states altered so that most flies behave according to our direction. Our recent studies have revealed a role for distinct subsets of dopaminergic neurons that innervate a brain region called the mushroom bodies in reward learning, memory re-evaluation and the control of motivated behavior. Although it is recognised that new gene expression is required to form persistent memories, and molecules are the targets of all therapeutic drugs in medicine, the relevant cellular sites of action often remain obscure. Knowing where memories are located in the fly brain therefore makes it possible to gain molecular level insight, with a unique perspective of being embedded within a relevant cell-specific context, of how a brain operates to alter behavior in response to rewards and internal state. Until recently, most studies of gene expression in the brain have pooled messenger RNAs purified from the entire brain, dissected regions, or small populations of fluorescently labeled material. Cell-specific expression and responses are therefore obscured by averaging signals from, often heterogeneous, collections of cells and cell-types. We will use cutting-edge Drop-seq, which permits simultaneous collection of transcriptomes from thousands of individually identified cells by first capturing each cell with a unique oligonucleotide-coated bead in a nanolitre volume reaction droplet. Our experiments will therefore provide an unprecedented individual celllevel view of transcriptional responses to memory formation and maintenance and are likely to be of broad importance and interest, given the evident conservation of gene function.