A closed-loop optogenetic screen for neurons controlling feeding in Drosophila.

Feeding is an essential part of animal life that is greatly impacted by the sense of taste. Although the characterization of taste-detection at the periphery has been extensive, higher order taste and feeding circuits are still being elucidated. Here, we use an automated closed-loop optogenetic activation screen to detect novel taste and feeding neurons in Drosophila melanogaster. Out of 122 Janelia FlyLight Project GAL4 lines preselected based on expression pattern, we identify six lines that acutely promote feeding and 35 lines that inhibit it. As proof of principle, we follow up on R70C07-GAL4, which labels neurons that strongly inhibit feeding. Using split-GAL4 lines to isolate subsets of the R70C07-GAL4 population, we find both appetitive and aversive neurons. Furthermore, we show that R70C07-GAL4 labels putative second-order taste interneurons that contact both sweet and bitter sensory neurons. These results serve as a resource for further functional dissection of fly feeding circuits.

Lau CKS ，Jelen M ，Gordon MD 《G3-Genes Genomes Genetics》

A subset of brain neurons controls regurgitation in adult Drosophila melanogaster.

Taste is essential for animals to evaluate food quality and make important decisions about food choice and intake. How complex brains process sensory information to produce behavior is an essential question in the field of sensory neurobiology. Currently, little is known about higher-order taste circuits in the brain as compared with those of other sensory systems. Here, we used the common vinegar fly, Drosophila melanogaster, to screen for candidate neurons labeled by different transgenic GAL4 lines in controlling feeding behaviors. We found that activation of one line (VT041723-GAL4) produces 'proboscis holding' behavior (extrusion of the mouthpart without withdrawal). Further analysis showed that the proboscis holding phenotype indicates an aversive response, as flies pre-fed with either sucrose or water prior to neuronal activation exhibited regurgitation. Anatomical characterization of VT041723-GAL4-labeled neurons suggests that they receive sensory input from peripheral taste neurons. Overall, our study identifies a subset of brain neurons labeled by VT041723-GAL4 that may be involved in a taste circuit that controls regurgitation.

Chen YD ，Ahmad S ，Amin K ，Dahanukar A ... -  《-》

Identification of a GABAergic neuroblast lineage modulating sweet and bitter taste sensitivity.

In Drosophila melanogaster, processing of gustatory information and controlling feeding behavior are executed by neural circuits located in the subesophageal zone (SEZ) of the brain.1 Gustatory receptor neurons (GRNs) project their axons in the primary gustatory center (PGC), which is located in the SEZ.1,2,3,4 To address the function of the PGC, we need detailed information about the different classes of gustatory interneurons that frame the PGC. In this work, we screened large collections of driver lines for SEZ interneuron-specific labeling and subsequently used candidate lines to access the SEZ neuroblast lineages. We converted 130 Gal4 lines to LexA drivers and carried out functional screening using calcium imaging. We found one neuroblast lineage, TRdm, whose neurons responded to both sweet and bitter tastants, and formed green fluorescent protein (GFP) reconstitution across synaptic partners (GRASP)-positive synapses with sweet sensory neurons. TRdm neurons express the inhibitory transmitter GABA, and silencing these neurons increases appetitive feeding behavior. These results demonstrate that TRdm generates a class of inhibitory local neurons that control taste sensitivity in Drosophila.

Zhao Y ，Duan J ，Han Z ，Engström Y ，Hartenstein V ... -  《-》

Closed-loop optogenetic activation of peripheral or central neurons modulates feeding in freely moving Drosophila.

Manipulating feeding circuits in freely moving animals is challenging, in part because the timing of sensory inputs is affected by the animal's behavior. To address this challenge in Drosophila, we developed the Sip-Triggered Optogenetic Behavior Enclosure ('STROBE'). The STROBE is a closed-looped system for real-time optogenetic activation of feeding flies, designed to evoke neural excitation coincident with food contact. We previously demonstrated the STROBE's utility in probing the valence of fly sensory neurons (Jaeger et al., 2018). Here we provide a thorough characterization of the STROBE system, demonstrate that STROBE-driven behavior is modified by hunger and the presence of taste ligands, and find that mushroom body dopaminergic input neurons and their respective post-synaptic partners drive opposing feeding behaviors following activation. Together, these results establish the STROBE as a new tool for dissecting fly feeding circuits and suggest a role for mushroom body circuits in processing naïve taste responses.

Musso PY ，Junca P ，Jelen M ，Feldman-Kiss D ，Zhang H ，Chan RC ，Gordon MD ... -  《eLife》

Identification of neurons responsible for feeding behavior in the Drosophila brain.

Sun F ，Wang Y ，Zhou Y ，Van Swinderen B ，Gong Z ，Liu L ... -  《-》