Biology subjects

Cascino-Milani, F.

Publications and source records attributed to Cascino-Milani, F..

3 recordsLinked to original sources

bioRxiv2025

Control of walking direction by descending and dopaminergic neurons in Drosophila

Animals need to fine-control the speed and direction of locomotion to navigate complex and dynamic environments. To achieve this, they integrate multimodal sensory inputs with their internal drive to constantly adjust their motor output. This integration involves the interplay of neuronal populations across different hierarchical levels along the sensorimotor axis - from sensory, central, and modulatory neurons in the brain to descending neurons and motor networks in the nerve cord. Here, we characterize two populations of neurons that control distinct aspects of walking on different hierarchical levels in Drosophila. First, we use in-vivo electrophysiological recordings to demonstrate that moonwalker descending neurons (MDN) integrate antennal touch to drive changes in walking direction from forward to backward. Second, we establish DopaMeander as an important component in the control of forward walking through a combination of optogenetic activation, silencing, connectomics, and in-vivo recordings. These dopaminergic modulatory neurons drive forward walking with increased turning, and the activity of individual neurons is correlated with ipsiversive turning. Hence, MDN and DopaMeander control opposite regimes of walking on different hierarchical levels. Computational models reveal that their activity predicts key parameters of spontaneous walking. Moreover, we find that both MDN and DopaMeander are gated out during flight. This suggests that neuronal populations across levels of control are modulated by the behavioral state to minimize cross-talk between motor programs.

neuroscience↗

bioRxiv2024

Nutritional state-dependent modulation of Insulin-Producing Cells in Drosophila

Insulin plays a key role in metabolic homeostasis across vertebrate and invertebrate species. Drosophila Insulin-Producing Cells (IPCs) are functional analogues to mammalian pancreatic beta cells and release insulin directly into circulation. IPC activity is modulated by nutrient availability, circadian time, and the behavioral state. To investigate the in vivo dynamics of IPC activity in the context of metabolic homeostasis, we quantified effects of nutritional and internal state changes on IPCs using electrophysiological recordings. We found that the nutritional state strongly modulates IPC activity. IPCs became less active with increasing periods of starvation. Refeeding starved flies with glucose or fructose, two nutritive sugars, significantly increased IPC activity, whereas non-nutritive sugar and protein had no effect. In contrast to feeding, glucose perfusion did not affect IPC activity. This was reminiscent of the mammalian incretin effect, in which ingestion of glucose drives higher insulin release than intravenous glucose application. Contrary to IPCs, Diuretic hormone 44-expressing neurons in the pars intercerebralis (DH44PINs), which are anatomically similar to IPCs, responded to glucose perfusion. Functional connectivity experiments demonstrated that glucose-sensing DH44PINs do not affect IPC activity, while other DH44Ns inhibit IPCs. This suggests that populations of autonomously and systemically sugar-sensing neurons work in parallel to maintain metabolic homeostasis. Ultimately, metabolic state changes affect behavior. For example, hungry flies increase their locomotor activity in search of food. In support of this idea, activating IPCs had a small, satiety-like effect on starved flies, resulting in reduced walking activity, whereas activating DH44Ns strongly increased walking activity. Taken together, we show that IPCs and DH44Ns are an integral part of a sophisticated modulatory network that orchestrates glucose homeostasis and adaptive behavior in response to shifts in the metabolic state.

neuroscience↗

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↗