Single cell correlates of memory, motivation and individuality

Directed behavior emerges from neural integration of sensory stimuli, memory of prior experience andinternal states. We seek an understanding of these conserved neural mechanisms using genetically-encodedtools and the relatively small brain of the fruit fly Drosophila. By temporally controlling neural functionmemories 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 brainregion called the mushroom bodies in reward learning, memory re-evaluation and the control of motivatedbehavior. Although it is recognised that new gene expression is required to form persistent memories, andmolecules are the targets of all therapeutic drugs in medicine, the relevant cellular sites of action oftenremain obscure. Knowing where memories are located in the fly brain therefore makes it possible to gainmolecular 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, moststudies of gene expression in the brain have pooled messenger RNAs purified from the entire brain, dissectedregions, or small populations of fluorescently labeled material. Cell-specific expression and responses aretherefore obscured by averaging signals from, often heterogeneous, collections of cells and cell-types. Wewill use cutting-edge Drop-seq, which permits simultaneous collection of transcriptomes from thousands ofindividually identified cells by first capturing each cell with a unique oligonucleotide-coated bead in ananolitre volume reaction droplet. Our experiments will therefore provide an unprecedented individual celllevelview of transcriptional responses to memory formation and maintenance and are likely to be of broadimportance and interest, given the evident conservation of gene function.