How we perceive, move, feel, learn, and remember is a product of the ability of nerve cells to form circuits that allow an extraordinarily fast and precise communication processing information. Information is transferred from cell to cell through specialized cell-cell contact sites, termed synapses. Despite tremendous advances, understanding the molecular mechanisms facilitating, maintaining and/or re-arranging synaptic function and/or structure remains a key problem in contemporary neuroscience. Using a genetic approach, we identified a new protein (WD40A) that is very similar from fruit flies to humans. We hypothesize that WD40A may control the protein levels of another uncharacterized protein (ATP8B) that may control the lipid (i.e., fatty acid) composition of the synaptic membranes that facilitate information transfer from one nerve cell to another. To better support this hypothesis, the role and significance of WD40A for synaptic function and structure will be explored using electrical and optical recordings to examine the effects of genetic mutations in WD40A on synaptic function. In addition, genetic and biochemical approaches will be used to characterize exactly how WD40A controls ATP8B protein levels at synapses. The project will develop valuable research tools that will be made freely available to the research community and will provide research opportunities for both graduate and undergraduate students. This work is expected to characterize a fundamentally new molecular mechanism that induces local changes in the lipid environment of synapses aiding rapid communication among nerve cells. This knowledge will significantly advance our understanding of how the brain is able to compute information on a millisecond scale, and improve our ability to design better medical approaches to treat or prevent some neurological disorders in humans.
