Balles, I. S. | bioRxiv Science

bioRxiv2025

A novel enteric pacemaker activity in Drosophila

Enteric organs such as the gut and stomach display the intrinsic ability to generate slow-wave potentials, rhythmic electrochemical events acting as key regulators of gastrointestinal motility. In mammals, slow waves occur as a result of the pacemaker activity of Interstitial Cells of Cajal (ICCs) which, by recruiting visceral muscles, ultimately lead to peristalsis. Here, we uncover and characterize a novel mechanism in Drosophila by which the midgut is able to generate strong muscular whip-like contractions. This pacemaker activity, here named superstalsis, is only active at certain physiological conditions and is selectively linked to longitudinal visceral muscle activation. Furthermore, we identify in Subdued, an ortholog gene of the ANO1/TMEM16A family, a marker for peristalsis in Drosophila, specifically associated with circular muscle activity. As fasting and bacterial infections cause specific changes in the intestinal motility profiles in vivo, we propose that the gut can autonomously alter the peristalsis/superstalsis balance to efficiently respond to diverse pathological and homeostatic events.

physiology↗

bioRxiv2023

Aminergic and peptidergic modulation of Insulin-Producing Cells in Drosophila

Insulin plays a critical role in maintaining metabolic homeostasis. Since metabolic demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments are mediated by different pathways, most prominently the blood glucose level, but also by feedforward signals from motor circuits and different neuromodulatory systems. Here, we analyze how neuromodulatory inputs control the activity of the main source of insulin in Drosophila - a population of Insulin-Producing Cells (IPCs) located in the brain. IPCs are functionally analogous to mammalian pancreatic beta cells, but their location makes them accessible for in vivo recordings in intact animals. We characterized functional inputs to IPCs using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, and an optogenetics-based intrinsic pharmacology approach. Our results show that the IPC population expresses a variety of receptors for neuromodulators and classical neurotransmitters. Interestingly, IPCs exhibit heterogeneous receptor profiles, suggesting that the IPC population can be modulated differentially. This is supported by electrophysiological recordings from IPCs, which we performed while activating different populations of modulatory neurons. Our analysis revealed that some modulatory inputs have heterogeneous effects on the IPC activity, such that they inhibit one subset of IPCs, while exciting another. Monitoring calcium activity across the IPC population uncovered that these heterogeneous responses occur simultaneously. Certain neuromodulatory populations shifted the IPC population activity towards an excited state, while others shifted it towards inhibition. Taken together, we provide a comprehensive, multi-level analysis of neuromodulation in the insulinergic system of Drosophila.

neuroscience↗