Neural and Molecular Basis of Individual Differences in Brain Function and Behavior

PROJECT SUMMARY A fundamental goal of neuroscience is to determine how different brain regions contribute to behavior (i.e. structure-function relationships). Although significant progress has been made in discovering regional functions that are common across individuals, we know little about how structure-function relationships differ between individuals. Recent evidence suggests that there are many such individual differences in brain activity, with factors like genetics and sex have outsize influence on patterns of brain activity. But the molecular basis of these differences, and their consequences for behavior, are unknown. To begin exploring this new territory, we will (1) identify brain regions whose relationship to behavior is influenced by genetics and sex, and (2) identify neurotransmitters and receptors that underlie the influence of genes and sex on brain function and behavior. We will do this by measuring patterns of whole-brain activity that underlie exploratory behavior and long-term memory recall in adult zebrafish. Zebrafish are a genetically tractable animal model with several characteristics that make them ideal for the present research: a small and simple morphology, a sophisticated behavioral repertoire, and ease of genetic manipulation. As vertebrates, zebrafish retain a high similarity to mammals in genetics and nervous system organization. Given that many mental health disorders manifest as alterations in patterns of neural activity, understanding how individual differences in biology influence brain function and behavior will inform the development of precision approaches for the treatment of disorders localized to the brain.