Why individuals behave differently from one another is an enduring question in behavioral neuroscience. Every individual is a product of unique genetics, environment, experience and developmental contingencies. How these differences play out to produce individual behavior is currently unknown. This project aims to study the origins of individuality in behavior using the genetic model system Drosophila melanogaster, which permits holding genetics, environment and experience constant across individuals. Nevertheless behavioral diversity on odor-evoked behaviors is abundant in these experimental populations. The molecular and neural circuit mechanisms underlying these individual differences will be investigated using the tools of modern behavioral neuroscience, including high-throughput behavioral testing, pharmacological manipulation to identify critical neuromodulatory effects and neurotransmitters, and imaging to record neural activity. Preliminary evidence suggests that each individual encodes odor information differently. That is, behavioral differences may arise because each individual senses its olfactory environment differently. The mechanisms underlying these differences in stimulus encoding will be the focus of investigation. The principles uncovered are likely applicable in humans as well, given the commonalities of molecular biology across animal species. In order to broadly communicate these principles, and encourage student STEM engagement, the PI will collaborate with the DNA Learning Center of Cold Spring Harbor Laboratory to develop and distribute odor preference kits for high school students. These will allow students to measure variation in their own odor preference and investigate its origin in genetic differences in olfactory receptors.
The objective of this project is to identify the neural underpinnings of the intragenotypic variability in odor-evoked behavior using a uniquely accessible system - the early olfactory circuit of the fruit fly, Drosophila melanogaster. Building on tools developed in their laboratory, a combined approach of behavioral and neurophysiological characterization will be used to determine the: 1) degree of idiosyncrasy in flies' odor preferences, 2) ways in which odor coding varies between individuals, and 3) behavioral consequences of this neurophysiological variation. In flies, the olfactory system is coarsely hardwired, with neurons that are anatomically and genetically identifiable across different individuals. Despite this stereotypy, individual odor preference is quite variable across flies - as in humans. Likewise, the neural coding of odor varies between flies. The relationship between these dimensions of variation is unknown, but can be elucidated by identifying neural coding features that predict behavioral tendencies. First, their behavioral assay will be extended to measure multidimensional odor preferences of individual flies. Second, subcellular-resolution functional imaging will quantify across-fly variation in neural coding in olfactory sub-circuits. Third, these approaches will be combined by recording neural activity in animals that have been first measured for behavioral preferences to assess which idiosyncratic neural activity signals are predictive of idiosyncratic odor preferences.
