Proteomics, Actin and Plasticity in Circadian Rhythms

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How does the brain encode experience so that future behaviors are changed? Altered neural function that long outlasts experience characterizes brain processes from learning to memory modification to resetting the circadian clock, which patterns behavioral changes over the day-night cycle. Underlying mechanisms are not understood. Consensus is emerging that stimulus-induced remodeling of the actin-based cellular architecture redistributes key informational proteins bound there. Which proteins mediate this change? The researcher will use the power of the mammalian circadian clock, where mechanisms, including plasticity, are evolutionarily ancient and conserved, and control of the rhythmic homeostatic patterning of daily behaviors is localized within one brain site, the suprachiasmatic nucleus (SCN). They will employ a cross-disciplinary approach, combining novel analytical chemistry that enables large-scale analysis and identification of actin-binding proteins in local brain regions with neurophysiology and behavior. The researcher will manipulate SCN actin state, comparing effects of natural neural signals on actin-associated proteins with reagents that directly activate or inhibit actin remodeling. This broad approach will permit discovery of protein complexity necessary for circadian neural and behavioral plasticity. Coupled proteomic and functional analyses will provide new insights on how sensory experience is integrated into a long-lasting response spanning molecular, cellular, brain and behavioral levels. Research on this evolutionarily ancient brain system will identify a set of core plasticity elements that may contribute critical emergent properties to all forms of brain plasticity. Thus, findings will impact understanding of fundamental principles of experience-induced brain adaptation. Beyond scientific inquiry, this study will provide training opportunities at the intersection of analytical chemistry and neuroscience for students in the laboratory, as well as outreach to undergraduates, especially minorities under-represented in science.