RobustCircuit Project 8

Sex-specific differences in the variability of Dorsal Cluster Neuron branching lead to sexually dimorphic wiring asymmetry and behavior

Gerit Linneweber

Imprecision: DCN wiring patterns develop independently and variably between the left and right brain hemispheres.  Developmental imprecisions are higher in males than females.

Robustness: The outcomes of the DCN developmental process are robustly different distributions for left/right asymmetry and, correspondingly, behavior in males and females Hypothesis: Increased developmental imprecision specifically in male brains leads to increased DCN asymmetry and thereby increased visual attention behavior on average in males.

Hypothesis: Variability of intrinsic neuronal properties and electrical coupling is not detrimental, but rather supports a stable network splay state for efficient activation of flight muscles with a potentially reduced requirement for complex regulatory control.

Project Summary

DCN axon branches and synaptically connected neurons

In sexually dimorphic animals, males and females display qualitative differences in behavior, usually related to courtship and reproduction. Additionally, males and females exhibit quantitative differences for behaviors shared by both sexes. For example, both male and female Drosophila exhibit visual fixation behavior in Buridan’s paradigm, but female behavior is on average more ‘exploratory’ while male behavior is on average more ‘fixated’. My recent work has shown that increasing asymmetry of axonal projections of contralaterally projecting interneurons, the Dorsal Cluster Neurons (DCNs), leads to increased visual fixation behavior. In preliminary work for RobustCircuit, I have shown that there is indeed a higher asymmetry of DCN axonal projections in males compared to females. Since the development of DCN projection patterns includes intrinsically stochastic, non-heritable processes, these preliminary observations give rise to a surprising hypothesis: Male DCN wiring asymmetry (and consequently increased visual fixation behavior) are the consequence of a male-specific increase in the variability of developmental processes determining DCN branching patterns. An increase of DCN branching variability on the left and right side of the brain causes a rise of the average asymmetry and leads to sex-specific distributions of individually probabilistic behaviors. I hypothesize that male and female populations consist of individuals with a wide range of randomly unique, non-heritable behavior, while on average, genetic determinants in males shift the distribution average to more fixated visual orientation behavior. P8 will interrogate the sex-specific mechanisms underlying this distribution shift. When this work is concluded, I will have tested how the robust development of sexually dimorphic behavioral distributions is achieved through a genetically encoded increase in branching variability in males compared to females.

References

  1. Kiral, F.R., Dutta, S.B., Linneweber, G.A., Poppa, C., Duch, C., von KLeist, M., Hassan, B.A., and Hiesinger, P.R. (2021). Brain Connectivity inversely scales with developmental temperature in Drosophila, Cell Rep. 37(12):110145.
  2. Kiral FR, Linneweber GA, Mathejczyk T, Georgiev SV, Wernet MF, Hassan BA, von Kleist M, Hiesinger PR (2020). Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring. Nat. Commun.12;11(1):1325. doi:10.1038/s41467-020-14781-4.
  3. Linneweber GA, Andriatsilavo M, Bias Dutta S, Bengochea M, Hellbruegge L, Liu G,Ejsmont RK, Straw AD, Wernet MF, Hiesinger PR, Hassan BA (2020). A neurodevelopmental origin of behavioral individuality in the Drosophila visual system. Science 367(6482), 1112-1119, DOI: 10.1126/science.aaw7182
  4. Liu G, NathT, Linneweber GA, Guo, Z, Li, Z, De Backer S, Weyn B, Sneyders M, Nicasy H, Yu P, Scheunders P, Hassan BA (2018). A novel tracking and quantitative social network analysis pipeline reveals the effects of isolation on social interaction dynamics in Drosophila. Plos Comp Biol, 14(8):e1006410
  5. Linneweber GA,Winking M, Fischbach KF (2015). The Cell Adhesion Molecules Roughest, Hibris, Kin of Irre and Sticks and Stones Are Required for Long Range Spacing of the Drosophila Wing Disc Sensory Sensilla. PLoS One. 8;10(6):e0128490
  6. Linneweber GA, Jacobson J, Busch KE, Hudry B, Christov CP, Dormann D, Yuan M, Otani T, Knust E, de Bono M, et al. (2014). Neuronal Control of Metabolism through Nutrient-Dependent Modulation of Tracheal Branching. Cell 156, 69-83.