Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
OX1 2JD Oxford
Regno Unito