Wappner, M. | Search bioRxiv

bioRxiv2024

Neuronal synchronization in Drosophila

Rhythms are intrinsic to biological processes across temporal and spatial scales. In the brain, the synchronized oscillatory activity of neurons creates collective rhythms that are essential for complex functions. While this is a recognized phenomenon in the mammalian brain, information about insect neuronal synchrony and its underlying mechanisms is scarce. In the fly brain, neuronal oscillations were reported in individual lateral ventral neurons (LNvs), which play a key role in circadian and sleep behaviors. However, it is still unclear whether and how these participate in a collective rhythm. In this work, we perform thorough whole-cell patch clamp recordings of LNvs, and demonstrate consistent membrane potential oscillations. We show that oscillations degrade over time, and disappear upon exposure to an acetylcholine receptor blocker. Together with a flat phase response curve, these results suggest that oscillations are exogenously produced. Prompted by these results, we propose a generic forced oscillator theory that can account for the experimental phase response. The theory further predicts that neurons with similar properties should oscillate in synchrony with zero lags, while neurons with different properties may show coherent oscillations with non-zero lags. We confirm this prediction through simultaneous patch clamp recordings of neuronal pairs, revealing that large LNvs are consistently advanced relative to small LNvs. Additionally, we find that other neurons in the accessory medulla also exhibit coherent membrane potential oscillations, with diverse lags. Our findings suggest the intriguing possibility that brain waves may arise from collective neuronal activity within this region of the fly brain.

neuroscience↗

bioRxiv2024

Multiple Notch ligands in the synchronization of the segmentation clock

Notch signaling is a ubiquitous and versatile intercellular signaling system that drives collective behaviors and pattern formation in biological tissues. During embryonic development, Notch is involved in generation of collective biochemical oscillations that form the vertebrate body segments, and its failure results in embryonic defects. Notch ligands of the Delta family are key components of this collective rhythm, but it is unclear how different Delta ligands with distinct properties contribute to relaying information among cells. Motivated by the zebrafish segmentation clock, in this work we propose a theory describing interactions between biochemical oscillators, where Notch receptor is bound by both oscillatory and nonoscillatory Delta ligands. Based on previous in vitro binding studies, we first consider Notch activation by Delta dimers. This hypothesis is consistent with experimental observations in conditions of perturbed Notch signaling. Then we test an alternative hypothesis where Delta monomers directly bind and activate Notch, and show that this second model can also describe the experimental observations. We show that these two hypotheses assign different roles for a non-oscillatory ligand, as a binding partner or as a baseline signal. Finally, we discuss experiments to distinguish between the two scenarios. Broadly, this work highlights how a multiplicity of ligands may be harnessed by a signaling system to generate versatile responses.

developmental biology↗