Behavioral state-dependent modulation of insulin-producing cells in Drosophila

Liessem, Sander; Held, Martina; Bisen, Rituja S; Haberkern, Hannah; Lacin, Haluk; Bockemühl, Till; Ache, Jan Marek

doi:10.1016/j.cub.2022.12.005

Cited by 11 publications

(22 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To investigate how the electrophysiological activity recorded in patch-clamp translates into calcium signals in IPCs, we recorded the spontaneous base-line activity from one IPC via patch-clamp while performing calcium imaging of 13 IPC cell bodies (ROIs) without activating any MNs. When comparing the membrane potential with the fluorescence traces of the same IPC, it became evident that fluorescence increases matched the occurrence of action potentials faithfully (Figure 4J, gray boxes and purple traces), as indicated before for IPCs (Liessem et al, 2023). Accordingly, a burst of action potentials led to a prolonged and stronger calcium influx (Figure 4J asterisks).…”

Section: Resultssupporting

confidence: 76%

“…For example, OA drives increases in locomotor activity and foraging behavior while insulin decreases these behaviors (Brembs et al, 2007; Yang et al, 2015; Yu et al, 2016). Accordingly, OA is released during increased physical activity, such as flight and walking, while insulin release is inhibited (Brembs et al, 2007; Suver et al, 2012; Liessem et al, 2023). Moreover, knockdown of the OAMB receptor in IPCs resulted in increased Dilp2 expression (Luo et al, 2014; Li et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…This would enable a moderate insulin release upon arrival of a secondary excitatory input (Figure 5E). On the other hand, an additional inhibitory input would lead to a drastic shut down of IPC activity (Figure 5E) as observed during locomotion (Liessem et al, 2023). 3) The heterogeneous input could regulate the ratio of DILP2, 3, and 5 release.…”

Section: Ipcs Form a Heterogeneous Population That Is Differentially ...mentioning

confidence: 90%

“…2) IPCs are modulated by different neuronal networks to adjust DILP release according to internal states, metabolic demands, and external inputs (Nässel et al, 2013; Nässel & Zandawala, 2020; Liessem et al, 2023). 3) IPCs have been characterized in the brain connectome, facilitating comparisons between modulatory and synaptic inputs (Reinhard et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Aminergic and peptidergic modulation of Insulin-Producing Cells inDrosophila

Held,

Bisen,

Zandawala

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Insulin plays a critical role in maintaining metabolic homeostasis. Since metabolic demands change momentarily, insulin release needs to be constantly adjusted. These adjustments are mediated via distinct pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits, and different neuromodulatory pathways. Here, we analyzed 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 the functional inputs to IPCs using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, 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, individual IPCs exhibit heterogeneous receptor profiles, suggesting they could be modulated differentially. This is supported by electrophysiological recordings of IPCs which we performed while activating different populations of modulatory neurons. Our analysis revealed that some modulatory inputs had heterogeneous effects on the IPC activity, such that they inhibited one subset of IPCs, while exciting another. Monitoring calcium activity across the IPC population revealed that these heterogeneous responses occurred simultaneously. Certain neuromodulatory populations shifted the IPC population activity towards an excited state, while others shifted the IPCs towards inhibition. Taken together, we provide a comprehensive, multi-level framework of neuromodulation in the insulinergic system of Drosophila.

show abstract

Section: Resultssupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Ipcs Form a Heterogeneous Population That Is Differentially ...mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aminergic and peptidergic modulation of Insulin-Producing Cells inDrosophila

Held,

Bisen,

Zandawala

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Command neurons were initially identified in reduced preparations in crustaceans, but their precise function in the intact animal was unknown. Experimental work uniquely possible in insects has the potential to further refine and extend principles of nervous system organization, particularly when combined with eletrophysiological approaches such as patch-clamp recording (Liessem et al 2022). Such advanced techniques will improve our understanding of the insect nervous system, which may further increase the neuromorphic nature of hexapod robot controllers.…”

Section: Experimental Opportunities With Insectsmentioning

confidence: 99%

A perspective on the neuromorphic control of legged locomotion in past, present, and future insect-like robots

Szczecinski

Goldsmith

Nourse

et al. 2023

Neuromorph. Comput. Eng.

View full text Add to dashboard Cite

This article is a historical perspective on how the study of the neuromechanics of insects and other arthropods has inspired the construction, and especially the control, of hexapod robots.Many hexapod robots’ control systems share common features, including:1. Direction of motor output of each joint (i.e., to flex or extend) in the leg is gated by an oscillatory or bistable gating mechanism; 2. The phasing between each joint is influenced by proprioceptive feedback from the periphery (e.g., joint angles, leg load) or central connections between joint controllers; and3. Behavior can be directed (e.g., walking along a curved path) via low-dimensional, broadly-acting descending inputs to the network.These distributed control schemes are inspired by, and in some robots, closely mimic the organization of the nervous systems of insects, the natural hexapods, as well as crustaceans. Nearly a century of research has revealed organizational principles such as central pattern generators (CPGs), the role of proprioceptive feedback in control, and command neurons.These concepts have inspired the control systems of hexapod robots in the past, in which these structures were applied to robot controllers with neuromorphic (i.e., distributed) organization, but not neuromorphic computational units (i.e., neurons) or computational hardware (i.e., hardware-accelerated neurons). Presently, several hexapod robots are controlled with neuromorphic computational units with or without neuromorphic organization, almost always without neuromorphic hardware. In the near future, we expect to see hexapod robots whose controllers include neuromorphic organization, computational units, and hardware. Such robots may exhibit the full mobility of their insect counterparts thanks to a “biology-first” approach to controller design.This perspective is not a comprehensive review of the neuroscientific literature but is meant to give a gentle introduction into the principles that underlie models and inspire neuromorphic robot controllers. Deeper reviews of particular topics from biology are suggested throughout.

show abstract