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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Molmechindividuality (Molecular mechanisms of neuronal connectivity - the synaptic code for variability and stereotypy)

Teaser

Summary

Individual differences even amongst genetically identical twins, implies the existence of intrinsic mechanisms to generate variability. This variability is often referred to as developmental noise. Developmental noise creates variability not only at the exterior morphology of animals, but it also creates variability of the nervous system. The contribution of these developmental imprecisions in nervous system development to individual behavior, in humans for personality remains largely unknown.
This important question on the origins of individual variation has major implications for the nature nurture debate and is a key question of the neurosciences and psychology. Given the central scientific importance of this question, providing a scientific answer progresses not only science, but also society. Additionally, to progressing societal knowledge answering questions about individual variations has also key implications to emerging fields as personalized medicine, underscoring the importance of individualized treatments of diseases.
My work demonstrated in the fruit fly Drosophila melanogaster that individual behavioral variation exists and to a similar degree individual variation in brain wiring. I could demonstrate that individual differences in brain wiring are functionally relevant and that differences in neuronal anatomy originating from stochastic developmental processes are important for the behavioral outcome by creating individual wiring diagrams.

Work performed

1. We established a screening method to use GRASP (GFP Reconstitution Across Synaptic Partners) to search for synaptic connectivity and connectivity mutations. We performed a candidate screen and found known and unknown determinants of wiring and neuronal function. One new factor that We identified in the Drosophila olfactory system was the Drosophila homologue of FMRP the causative gene of fragile X syndrome in humans (Franco et al., 2017).

2. We established a correlative analysis of circuit variability with behavioral variability and I could show that they are causally related to each other. Interestingly, we found especially asymmetry in neuronal wiring to have causal links for selective attention and therefore the behavioral outcome.

3. We established manipulations of circuit variability to alter the behavioral outcome. Using cell signaling pathways We were able to change a behaviorally relevant circuit and we were able to show that these changes on the circuit level alter behavior.

4. We published 2 research articles (listed below) in the course of the Marie SkÅ‚odowska-Curie Action and 3 more are in late stages before publication. We were part of several public engagement activities to promote science to the general public.

1. Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome
LM Franco, Z Okray, GA Linneweber, BA Hassan, E Yaksi
Current Biology 27
2. A simple computer vision pipeline reveals the effects of isolation on social interaction dynamics in Drosophila
G Liu, T Nath, GA Linneweber, A Claeys, Z Guo, J Li, M Bengochea, ...PLoS computational biology 14 (8), e1006410

Final results

The Marie SkÅ‚odowska-Curie Action Molmechindividuality has significantly progressed the fields of neurobiology and psychology by demonstrating that stochastic developmental mechanisms that shape the nervous system have an impact on the behavioral traits a given animal has. The use of invertebrate model organism allows to study these changes also in the context of health and disease. Therefore, these results might in the long run become highly relevant in the emerging fields of individualized medicine.