Biology subjects

Mendes, C. S.

Publications and source records attributed to Mendes, C. S..

6 recordsLinked to original sources

bioRxiv2025

Sex-specific control of locomotor behavior by neuronal Arhgef10 in aged Drosophila

Mutations and polymorphisms in the Rho guanine nucleotide exchange factor 10 (ARHGEF10) locus are associated with behavioral and locomotor dysfunctions in humans, including psychiatric disorders and polyneuropathies that show age- and sex-specific prevalence. ARHGEF10 encodes a conserved guanine exchange factor that activates Rho GTPases and has proposed roles in cell migration and adhesion, but the relevant cell types and mechanisms underlying its age- and sex-dependent effects remain unclear. Drosophila darhgef10 gene is the single orthologue of vertebrate ARHGEF10 and its paralogue ARHGEF10L. Here, to gain more direct insight into possible age- and sex-dependent ARHGEF10 neuromuscular functions, we generated darhgef10 knock-out flies and quantified induced walking kinematics with high-speed imaging and coarse spontaneous behaviors--walking, micromovements, rest, and sleep--in open arenas. Mutants of both sexes exhibited abnormal walking kinematics, which worsened with age in females. Cell-type-specific knockdowns indicated that locomotor phenotypes arose primarily from neuronal, rather than glial or muscle, requirements. dArhgef10 was especially critical in glutamatergic motor neurons of aged females. dArhgef10 was also required for wakefulness and activity initiation in females but, surprisingly, not in males. Genetic rescue and isoform expression analyses suggested that sexually-dimorphic expression of long isoforms RC and/or RD underlies at least part of the sex-specific requirements of dArhgef10 in locomotor behavior control, revealing unanticipated complexity in its activity regulation. Collectively, our results suggest ARHGEF10 plays an ancient, conserved role in neurons that promotes proper wakefulness and locomotor activity in an age- and sex-dependent manner.

animal behavior and cognition↗

bioRxiv2024

Covert muscle activity reveals dynamic freezing states and prepares the animal for action

When an animal detects a threat it must make a split-second choice between fight, flight or freezing (1-3). During freezing, skeletal muscles sustain tension to maintain rigid, sometimes atypical postures, for many minutes at a time (4). Meanwhile the animal must dynamically assess its surroundings to plan future actions and ready its body for movement. The interplay between the neural and somatic systems during freezing remains poorly understood. Here we show that freezing Drosophila melanogaster display a striking novel pattern of leg muscle activation unique to immobility, a rhythmic pulsing in the distal tibia. The muscle, which we show to be a previously undescribed leg accessory heart, displays multiple activity modes and ramps up to movement onset, implying a preparation for movement. The frequency of pulsing is dynamically modulated as the fly integrates external threat or safety cues, and artificially increasing pulse frequency leads to freezing breaks, indicating a causal role in the decision to move. Through the identification of a new Drosophila cardiac organ, this study provides a window into the multiple states which can underlie freezing behaviour, and the physiological changes which the body undergoes to ready the animal to move.

neuroscience↗

bioRxiv2022

Sustained spinal motor activity triggered by direct mechanosensory stimulation in adult Drosophila melanogaster

Most vertebrates and invertebrates such as Drosophila melanogaster are able to move in complex environments due to their ability to integrate sensory information along with motor commands. Mechanosensory structures exist along each leg to assist in motor coordination by transmitting external cues or proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers and their underlying circuits remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg Mechanosensory Bristles (MsB) and femoral Chordotonal Organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsB triggered sustained cyclic motor activity dependent only on circuits within the Ventral Nerve Cord (VNC). The duration of the MsB-induced movement was dependent on the number of excited cells and specific to leg afferents, since stimulation of MsB in other segments lead to different motor outcomes. MsB-mediated movement lacked inter and intra-leg coordination, but preserved antagonistic muscle activity within joints. Our data shows that sensory stimulation can act in combination with descending commands in order to elicit a faster response to mechanical stimulation. In addition, it sheds light on the ability of specific sensory circuits to modulate motor control, including initiation of movement, presenting a new system to better understand how different levels of coordination are controlled by VNC and central brain locomotor circuits. Significance StatementSensory feedback is critical to allow smooth and stable locomotion. Proprioceptors interact directly with pre-motor centers optimizing and sustaining coordinated movement. However, initiation of moment is considered to be triggered by higher-order centers in the brain. Here we took advantage of the genetic toolkit provided by the fruit fly Drosophila melanogaster to optogenetically activate different classes of leg sensory cells in immobile animals. We found that leg mechanosensory bristles can specifically trigger sustained leg activity independently of higher-order centers as headless flies could sustain prolonged leg movement upon mechanosensory stimulation. Moreover, while this sensory-evoked movement lacks intra- and inter-leg coordination, it still preserved basic antagonistic muscle activity. These findings suggest a parallel mechanism to trigger fast movement upon sensory stimulation. In addition, it provides a new model for movement initiation and a point-of-entry to define pre-motor circuits.

neuroscience↗

bioRxiv2021

Motor dysfunction in Drosophila melanogaster as a biomarker for developmental neurotoxicity

Humans interact with numerous chemical compounds with direct health implications, with several able to induce developmental neurotoxicity (DNT), which bear developmental, behavioral, and cognitive consequences from a young age. Current guidelines for DNT testing are notably costly, time consuming, and unsuitable for testing large numbers of chemicals. Therefore, there is a need for adequate alternatives to conventional animal testing for neurotoxicity and DNT. Here we show that detailed kinematic analysis can provide a strong indicator for DNT, using known (chlorpyrifos, CPS) or putative ({beta}-N-methylamino-L-alanine, BMAA) neurotoxic compounds. We exposed Drosophila melanogaster to these compounds during development and evaluated for common general toxicity -- notably developmental survival and pupal positioning, together with the FlyWalker system, a detailed adult kinematics evaluation method. At concentrations that do not induce general toxicity, the solvent DMSO had a significant effect on kinematic parameters. Nonetheless, CPS not only induced developmental lethality but also significantly impaired coordination in comparison to DMSO, altering 16 motor parameters, validating the usefulness of our kinematic approach. Interestingly, BMAA, although not lethal during development, induced a dose-dependent motor decay, targeting most parameters in young adult animals, phenotypically resembling normally aged, non-exposed flies. This effect was subsequently attenuated during ageing, indicating an adaptive response. Furthermore, BMAA induced an abnormal terminal differentiation of leg motor neurons, without inducing degeneration, underpinning the observed altered mobility phenotype. Overall, our results support our kinematic approach as a novel, highly sensitive and reliable tool to assess potential DNT of chemical compounds.

neuroscience↗

bioRxiv2021

Motor neuron boutons remodel through membrane blebbing

Wired neurons form new presynaptic boutons in response to increased synaptic activity, but the mechanism by which this occurs remains uncertain. The neuromuscular junction (NMJ) is a synapse formed between motor neurons (MNs) and skeletal muscle fibers and is critical for control of muscle contraction. Because Drosophila MNs have clearly discernible boutons that display robust structural plasticity, it is the ideal system in which to study bouton genesis. Here we show using ex-vivo and by live imaging that in response to depolarization, MNs form new boutons by membrane blebbing, a pressure-driven mechanism used in 3-D migration, but never described as a neuronal remodeling strategy. In accordance, F-actin is decreased during bouton growth (a hallmark of blebs) and we show that non-muscle myosin-II (a master regulator of blebbing) is recruited to newly formed boutons. Furthermore, we discovered that muscle contraction plays a mechanical role in activity-dependent plasticity, promoting bouton addition by increasing MNs confinement. Overall, we provide a novel mechanism by which established circuits create new boutons allowing their structural expansion and plasticity, using trans-synaptic physical forces as the main driving force. Understanding MN-muscle interplay during activity-dependent plasticity can help clarify the mechanisms leading to MN degeneracy observed in neuromuscular diseases.

cell biology↗

bioRxiv2020

Innate behavior sequence progression by peptide-mediated interorgan crosstalk

Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of fly larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.

animal behavior and cognition↗