The circuit variability underlying Drosophila behavioural individuality

• Applicant: Gerit Linneweber, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Developmental Neurobiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 452474683

My main research goal is to understand the contributions of genetic, stochastic and environmental factors to variation in brain wiring and behavioural individuality. The importance of this question to the neurosciences and psychology is highlighted by the classic and to this day ongoing “Nature versus Nurture” debate. Compared to genetic and environmental factors, the role of stochastic developmental processes is understudied. The goal of this proposal is to establish the role of intrinsically stochastic developmental processes during brain wiring in generating behavioural individuality.This proposal is based on my previous postdoctoral work, where I showed that stochastic developmental processes result in variable wiring diagrams in one class of neurons that contribute to individual behavioural traits. I now want to test for generality in other neurons as well as for other behaviours. In my recently published work, I described variability at the level of left/right asymmetries in a group of commissural neurons in the fly visual system called dorsal cluster neurons (DCNs) or lobular columnar neuron 14 (LC14). Using a single fly behavioural assay, I showed that flies display highly idiosyncratic responses that are very stable over long periods of time. This behavioural individuality is non-heritable and unaffected by genetic diversity. I used unbiased anatomy to behaviour correlation mapping to show that the DCN wiring asymmetry is a robust predictor of the behavioural performance of an individual fly. The more asymmetric the DCN wiring pattern, the narrower the path a fly moves between visual objects. These observations provide a tractable genetic and neuronal model for individuality.Based on my preliminary data from DCN neurons and the neural circuit they define, I would like to address two key open questions with my own research group: Question 1: Is DCN circuit variability exclusively determined by variability of DCN neurons, or is variability more general and other neurons in the circuit contribute to circuit variability as well? To answer this question, I propose: 1.1. An analysis of inter-individual variability in the fly visual system with a focus on the DCN circuitry. Question 2: Does the DCN circuit variability contribute to other visual and non-visual behavioural paradigms? To answer this question, I propose: 2.1. A DCN circuit variability analysis using additional visual assays. 2.2. A circuit variability analysis in a non-visual behavioural paradigm. Answering these two questions will provide key tests of generality: I hypothesize that (1) stochastic developmental processes are a general neuronal property affecting behaviour, and (2) that stochastic wiring differences affect several behaviours ranging from visual guided responses to activity patterns. When the experiments in this proposal are concluded, we will have determined how general stochastic neural circuit wiring affects individuality.

• DFG Programme: Independent Junior Research Groups