Biology subjects

Fox, J. L.

Publications and source records attributed to Fox, J. L..

5 recordsLinked to original sources

bioRxiv2025

Connectivity of serotonin neurons reveals a constrained inhibitory subnetwork within the olfactory system.

Inhibitory local interneurons (LNs) play an essential role in sensory processing by refining stimulus representations via a diverse collection of mechanisms. The morphological and physiological traits of individual LN types, as well as their connectivity within sensory networks, enable each LN type to support different computations such as lateral inhibition or gain control and are therefore ideal targets for modulatory neurons to have widespread impacts on network activity. In this study, we combined detailed connectivity analyses, serotonin receptor expression, neurophysiology, and computational modeling to demonstrate the functional impact of serotonin on a constrained LN network in the olfactory system of Drosophila. This subnetwork is composed of three LN types and we describe each of their distinctive morphology, connectivity, biophysical properties and odor response properties. We demonstrate that each LN type expresses different combinations of serotonin receptors and that serotonin differentially impacts the excitability of each LN type. Finally, by applying these serotonin induced changes in excitability to a computational model that simulates the impact of inhibition exerted by each LN-type, we predict a role for serotonin in adjusting the dynamic range of antennal lobe output neurons and in noise reduction in odor representations. Thus, a single modulatory system can differentially impact LN types that subserve distinct roles within the olfactory system. Significance StatementInhibitory interneurons refine information processing within sensory networks by enforcing distinct local computations. They are therefore ideal targets for modulatory neurons to efficiently alter sensory processing by up- or downregulating the computations each interneuron class subserves. We identify an interconnected network of three interneuron types in the olfactory system of Drosophila that receive a large amount of serotonergic synaptic input. Each interneuron type differs in their biophysical and response properties and serotonin differentially impacts their excitability. Finally, using a computational model, we predict that the combined effects of serotonin on these inhibitory neurons enables noise reduction in the olfactory system. Thus, modulation of individual cell types collectively adjusts distinct network computations to enable flexible sensory coding.

neuroscience↗

bioRxiv2024

Flies tune the sensitivity of their multifunctional gyroscope.

Locomotion requires navigating unpredictable and complex environments, demanding both stability and maneuverability within short timeframes. This is particularly important for flying insects, and the true flies (Diptera) stand out among this group for their impressive flight capabilities. Flies aerial abilities are partially attributed to halteres, tiny club-shaped structures that evolved from the hindwings and play a crucial role in flight control. Halteres oscillate during flight, in antiphase with the wings, providing rhythmic input to the wing steering system via arrays of embedded mechanosensors called campaniform sensilla. These sensor arrays convey timing information to the wing steering muscles, but linking haltere sensor location to sensor activity and the functional organization of the wing steering system remains a central challenge. Here, we use in vivo calcium imaging during tethered flight to obtain population-level recordings of the haltere sensory afferents in specific fields of sensilla. We find that haltere feedback is continuously modulated by visual stimuli to stabilize flight. Additionally, this feedback is present during saccades and help flies actively maneuver. We also find that the halteres multifaceted role arises from the steering muscles of the haltere itself, regulating haltere stroke amplitude to modulate campaniform activity. Taken together, our results underscore the crucial role of biomechanics in regulating the dynamic range of sensors and provide insight into how the sensory and motor systems of flies coevolved. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/583703v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1296750org.highwire.dtl.DTLVardef@13dc425org.highwire.dtl.DTLVardef@185de0org.highwire.dtl.DTLVardef@1bb38de_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Asynchronous haltere input impairs wing and gaze control in Drosophila

Halteres are multifunctional mechanosensory organs unique to the true flies (Diptera). A set of reduced hindwings, the halteres beat at the same frequency as the lift-generating forewings and sense inertial forces via mechanosensory campaniform sensilla. Though haltere ablation makes stable flight impossible, the specific role of wing-synchronous input has not been established. Using small iron filings attached to the halteres of tethered flies and an alternating electromagnetic field, we experimentally decoupled the wings and halteres of flying Drosophila and observed the resulting changes in wingbeat amplitude and head orientation. We find that asynchronous haltere input results in fast amplitude changes in the wing ("wing hitches"), but does not appreciably move the head. In multi-modal experiments, we find that wing and gaze optomotor responses are disrupted differently by asynchronous input. These effects of wing-asynchronous haltere input suggest that specific sensory information is necessary for maintaining wing amplitude stability and adaptive gaze control.

animal behavior and cognition↗

bioRxiv2021

Mitochondrial Contact Site and Cristae Organizing System (MICOS) Machinery Supports Heme Biosynthesis by Enabling Optimal Performance of Ferrochelatase

Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied, and all the biosynthetic enzymes have been structurally characterized to varying extents. Nevertheless, our understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Herein we investigate the molecular organization as well as the catalytic and structural features of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses reveal dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity and results in accumulation of highly reactive and potentially toxic tetrapyrrole precursors that may result in oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. Our data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis.

biochemistry↗

bioRxiv2021

Characterisation of FADD interactome reveals novel insights into FADD recruitment and signalling at the Death Inducing Signalling Complex (DISC)

Fas-associated death domain protein (FADD) plays a vital role in the extrinsic apoptotic pathway, where it forms an essential component of the death-inducing signaling complex (DISC). However, the precise early molecular events that facilitate recruitment of FADD to the DISC remain poorly defined. Using affinity purification and mass spectrometry we investigated the FADD interactome in untreated cells and following death receptor stimulation to identify novel FADD-interacting proteins. As expected, in death receptor-stimulated samples our analysis identified key components of the DISC such as Caspase-8. In addition, we identified novel binding partners including Transferrin Receptor 1 (TfR1) and Myosin Light Chain Kinase 2 (MYLK2) that are able to modulate FADD recruitment to the DISC and consequently downstream apoptotic signaling. TfR1 is pre-associated with FADD and recruited into the DISC; moreover, our data reveal that TfR1 is also pre-associated with the death receptors, TRAIL-R1 and TRAIL-R2, thereby functioning as a key regulator of DISC formation. In the case of MYLK2, specific binding of FADD to MYLK2 in non-apoptotic cells sequesters FADD from other DISC components ensuring aberrant apoptosis is not initiated. Furthermore, MYLK2 enzymatic activity is required to for it to translocate, in complex with FADD, to sites of DISC-mediated death receptor oligimerization. Taken together, our study highlights the important role that additional novel FADD binding partners play in the regulation of death receptor-mediated apoptotic cell death, in part by modulating FADD recruitment to the DISC.

biochemistry↗