RobustCircuit Project 4

Project 4 focuses on the role of imprecise connectivity between olfactory projection neurons and postsynaptic lateral horn neurons underlying innate behaviors.

Imprecision: Preliminary data indicate that the connectivity between olfactory projection neurons and lateral horn neurons is surprisingly imprecise.

Robustness: Lateral horn output governs robust innate behaviors at the level of individuals or at the level of the population – a distinction to be tested experimentally i

Hypothesis: Intrinsically probabilistic lateral horn connectivity ensures variability of specific behavioral functional parameters and thereby robustness to complex olfactory cues at the population level (bet hedging).

Project Summary

In a well-known example of stochastic wiring, projection neurons (PNs) in the olfactory system establish random connections between single glomeruli in the antennal lobe and Kenyon cells of the mushroom body. This random connectivity is considered necessary for learning. In contrast, the same PNs are considered to form more stereotypic connections with neurons of the lateral horn, which play a major role in driving innate behavior. P4 is motivated by recent findings, including my preliminary data, revealing surprising variability of the connectivity between PNs and lateral horn neurons. My analyses indicate that PNs develop inherently imprecise connections to the lateral horn and a computational model predicts that this imprecision can affect odor driven behavioral output, especially when odor information is transmitted through a single PN. These findings raise the question whether imprecise wiring is required to ensure variable functional output, similar to findings by RobustCircuit PIs for innate visual behavior (P8). It is not yet known whether variability of innate olfactory behaviors could be explained by PN-to-lateral horn connectivity; in preparation for RobustCircuit I have established the necessary assays to address this question. I hypothesize that intrinsically imprecise connectivity between PNs and lateral horn neurons underlies variability of an innate behavior and thereby ensures robustness and flexibility at the population level (bet hedging) in response to variable olfactory cues. However, the alternative hypothesis is equally interesting: if individual innate behaviors are invariant despite imprecise lateral horn connectivity, I hypothesize a role of this imprecision in maintaining a robust output response with respect to complex variable olfactory scenes, supported by recurrent connectivity in the lateral horn. The goal of P4 is to distinguish between these hypotheses through both experiments and computational modeling. When this work is concluded we will have characterized the hitherto little studied, and surprisingly variable, lateral horn connectivity across individuals and linked this variability in wiring to the robustness of innate behaviors at either the individual or population level.

References

1. Brandao, S.C., Silies, M., and Martelli, C. (2021). Adaptive temporal processing of odor stimuli. Cell Tissue Res. 383:125-141
2. Gorur-Shandilya, S., Martelli, C., Demir, M. & Emonet, T. (2019). Controlling and measuring dynamic odorant stimuli in the laboratory. J. Exp. Biol. doi:10.1242/jeb.207787
3. Martelli, C.*, Fiala, A. (2019). Slow presynaptic mechanisms that mediate adaptation in the olfactory pathway of Drosophila. eLife, doi:10.7554/eLife.43735. *corresponding author.
4. Martelli, C.*, Pech, U. *, Kobbenbring, S., Pauls, D. et al. (2017). SIFamide translates hunger signals into appetitive and feeding behavior in Drosophila. Cell Reports, 20, 464–478 * equal contribution.
5. Mathew D., Martelli C., Kelley-Swift E., Brusalis C., Gershow M., Samuel A., Emonet T., and Carlson J.R. (2013). Functional diversity among sensory receptors in a Drosophila olfactory circuit. Proc. Natl. Acad. Sci. USA, 110, E2134–E2143
6. Martelli C., Carlson J.R., Emonet T. (2013). Intensity Invariant Dynamics and Odor-Specific Latencies in Olfactory Receptor Neuron Response. Journal of Neuroscience 33, 6285–6297