Biology subjects

Warren, B.

Publications and source records attributed to Warren, B..

12 recordsLinked to original sources

bioRxiv2026

Discrete depolarisations of chordotonal organ neurons propagate toward the soma and are independent of the sensory TRP channels NompC and Nanchung-Inactive.

The electrophysiological process of auditory transduction in insects remains largely conjecture due to the unknown role of ion channels localised to the cilia, but experimental evidence supports either NompC or Nan-Iav as the auditory mechanotransduction ion channel. Here, we knocked down two key genes that code for the two candidate sound-activated ion channels using dsRNA-mediated RNA interference. We measured sound-evoked activity of the auditory nerve and intracellular electrical currents from the ciliated ending of individual auditory receptors. We found that the sound-evoked nerve activity was reduced in nompC, nan and ift88 knockdown. Using whole-cell patch clamp recordings we found that nompC and nan knockdown resulted in reduced sound-evoked transduction current. Stochastic depolarisations hypothesised to be mediated from one of the candidate mechanotransduction ion channels, either NompC or Nan-Iav, where not affected by knockdown of either channel. The discrete depolarisations are therefore mediated through another unidentified ion channel. We test the hypothesis that discrete depolarisations are graded action potentials that travel toward the soma through noise analysis of the transduction current and analysis of discrete depolarisations to voltage-steps. As a positive control we also knocked down ift88, a protein essential for transporting proteins, including ion channels, along the cilium and found both the transduction current and the discrete depolarisations decreased. Key pointsO_LIInjection of dsRNA decreased RNA of nompC and nan C_LIO_LISound-evoked nerve activity is reduced for RNAi-mediated knockdown of nompC and nan C_LIO_LINompC and Nan both contribute to the transduction current C_LIO_LIThe stochastic discrete depolarisations are not due to NompC or Nan-Iav ion channel but to a third unidentified ion channel. C_LIO_LINoise analysis of the transduction current and the discrete depolarisations suggests they are graded action potentials that travel in the direction of the soma. C_LIO_LIKnockdown of ift88 reduced both the transduction current and discrete depolarisations. C_LI Significance StatementInsects are important to understand, economically, agriculturally and medically. However, we still do not understand fundamental aspects of how insects detect their own body movements, vibrations and sound. These senses are detected by insect chordotonal organs, specialised miniaturised mechanoreceptors that convert movements into electrical signals through specialised ion channels. Previous experimental work has advocated either NompC or Nan-Iav as the mechanosensitive ion channel. Here, for the first time, we reduced the expression of both nompC and nan and measured the sound-evoked transduction current directly from neurons in a specialised auditory chordotonal organ. In contradiction to previous studies, we show that both ion channels contribute to the transduction current and find that electrical signals termed "discrete depolarisations" travel toward the soma.

neuroscience↗

bioRxiv2025

A sleep promoting role of phototransduction in Drosophila melanogaster

The daily sleep-wake cycle is a conserved behaviour defined by locomotion quiescence and enhanced responsive threshold to sensory stimuli. Both the circadian clock and sleep-homeostasis determine the daily sleep profile. Environmental light is a major sensory input and also regulates circadian clock and the balance between sleep and wakefulness. In Drosophila, the cellular mechanism and neural circuitry underlying light-mediated circadian synchronization are well-established, yet the direct relationship between light/visual input and sleep remains unclear. To address this knowledge gap, we measured sleep behaviour in Drosophila with mutations in genes involved in phototransduction and downstream neural transmission. We observed consistent day sleep fragmentation in flies with mutations in multiple phototransduction components. We also found that mutation that led to hyperpolarised Drosophila photoreceptors resulted in shorter day sleep. We found a severe reduction in locomotor speed in several visual mutants during normal waking time preventing assessment of their sleep-linked immobility. Taken together, our rigorous quantification of sleep in phototransduction genetic mutants reveals the key role of visual input in promoting sleep.

neuroscience↗

bioRxiv2025

Stretching of the insect mechanoreceptor evokes mechano-electrical transduction in auditory chordotonal neurons

Insects sound and vibration detection including proprioception rely on the scolopidium--a mechanosensory unit enclosing the sensory cilium of chordotonal organ neurons. The cilium, enclosed by a scolopale cell, contains mechanosensitive ion channels with the ciliary tip embedded in a cap. Despite knowledge of the scolopidial structure in multiple insects, the mechanism by which mechanical force elicits transduction remains speculative. We examined scolopidia in the auditory Mullers organ of the desert locust and present a comprehensive three-dimensional (3D) ultrastructure of a scolopidium using Focused Ion Beam Scanning Electron Microscopy (FIB-SEM). Next, we characterised sound-evoked motions of Mullers organ and the scolopidium using Optical Coherence Tomography (OCT) and high-speed light microscopy. Finally, we measured transduction currents via patch clamp electrophysiology during mechanical stimulation of individual scolopidia. By combining ultrastructure, sound-evoked motions, and transduction current recordings, our finding suggests that the scolopidium is activated best by stretch along the ciliary axis.

neuroscience↗

bioRxiv2024

Sex differences in auditory function of the desert locust

Age-related auditory decline manifests across the animal kingdom, from humans and mice to zebrafish and insects. Sex differences in auditory decline are established for humans, but there is now evidence in mice and even zebrafish. Here, we found sex differences in auditory decline in an insect, the Desert Locust and investigated its biological basis. We profiled gene expression in a dedicated auditory organ, Mullers organ to understand the genetic underpinning of sex differences and measured sound-evoked transduction currents and electrophysiological properties of auditory neurons to quantify auditory decline. We analysed gene expression in Mullers organ of young locusts where sex differences were absent and in older, noise-exposed locusts where sex differences were maximal. The largest differences in gene expression between the sexes was between young and stressed (aged and noise-exposed) auditory organs. We found sex-specific genes and gene ontology terms for juvenile hormone (JH) and sex-specific estrogen-related steroids. We hypothesise that sex differences in auditory decline are due to differences in hormones which then affect metabolic processes in and mitochondria. HighlightsO_LIFemale Desert Locusts have less auditory decline than males. C_LIO_LIFemales auditory organs maintain better metabolism under stressed conditions. C_LIO_LISex differences in gene expression are maximal during aging and noise-exposure. C_LIO_LISex differences are minimal between the sexes for young and stressed auditory organs. C_LI

neuroscience↗

bioRxiv2024

Hematophagy generates a convergent genomic signature in mosquitoes and sandflies

Blood-feeding (hematophagy) is widespread across Diptera (true flies), yet the underlying molecular mechanisms remain poorly understood. Using phylogenomics, we show that four gene families associated with neuro-modulation, immune responses, embryonic development, and iron metabolism have undergone independent expansions within mosquitoes and sandflies. Our findings illuminate the underlying genetic basis for blood-feeding adaptations in these important disease vectors.

evolutionary biology↗

bioRxiv2024

Molecular correlates of swarming behaviour in Aedes aegypti males.

Mosquitoes are the deadliest vectors of disease. They impose a huge health burden on human populations spreading parasites as disparate as protozoans (malaria), viruses (yellow fever and more), and nematodes (filariasis), which cause life-threatening conditions. In recent years, mating has been proposed as a putative target for population control. Mosquitoes mate mid-air in swarms initiated by males and triggered by a combination of internal and external stimuli. As the number of females in a swarm is limited, there is intense competition among males. Indeed, males retune their physiology for this demanding behaviour but the underlying genetic changes are largely unknown. Interestingly, recent evidence indicates that the upregulation of circadian clock genes may be involved in the swarming of malaria mosquitoes of the genus Anopheles. Here, we use whole-head RNA-seq to identify gene expression changes in Aedes aegypti males who are engaged in swarming in a laboratory setting. Our results suggest that swarming males tend to lower some housekeeping functions while increasing the remodelling of the cytoskeleton and neuronal connectivity; the transcription of circadian clock genes is unaffected.

genetics↗

bioRxiv2023

Effects of age and noise on tympanal displacement in the Desert Locust.

Insect cuticle is an evolutionary-malleable exoskeleton that has specialised for various functions. Insects that detect the pressure component of sound bear specialised sound-capturing tympani evolved from cuticular thinning. Whilst the outer layer of insect cuticle is composed of non-living chitin, its mechanical properties change during development and aging. Here, we measured the displacements of the tympanum of the desert Locust, Schistocerca gregaria, to understand biomechanical changes as a function of age and noise-exposure. We found that the stiffness of the tympanum decreases within 12 hours of noise-exposure and increases as a function of age, independent of noise-exposure. Noise-induced changes were dynamic with an increased tympanum displacement to sound within 12 hours post noise-exposure. Within 24 hours, however, the tone-evoked displacement of the tympanum decreased below that of control Locusts. After 48 hours, the tone-evoked displacement of the tympanum was not significantly different to Locusts not exposed to noise. Tympanal displacements reduced predictably with age and repeatably noise-exposed Locusts (every three days) did not differ from their non-noise-exposed counterparts. Changes in the biomechanics of the tympanum may explain an age-dependent decrease in auditory detection in tympanal insects.

biophysics↗

bioRxiv2023

Mechanically-evoked spike responses of pentascolopidial chordotonal organs of Drosophila larvae

Stretch-sensitive ensembles of neurons in insects, known as Chordotonal organs (COs), function in proprioception, the detection of sound and substrate vibrations. Here we characterize the mechanical sensitivity of the lateral pentascolopidial CO (lch5) of Drosophila larvae to establish its postulated role in proprioception. We developed a physiologically realistic method to replicate proprioceptive input to lch5 by pulling the apodeme (tendon) to which the tips of the neurons attach. We found that lch5 sensory neurons respond transiently with a short latency to the velocity-component of stretch displacements and the release of stretch (relaxation). The mechanosensory mutant inactive, has a decreased response to mechanical stimuli and a lower overall spontaneous spike rate. Finally, we simulated the input that lch5 receives during crawling and observed spikes coincident with the start, middle and end of each peristaltic body contraction. We provide the first characterization of proprioceptive feedback in Drosophila larvae and firmly establish the proprioceptive function of lch5 in larval locomotion. Summary statementWe have characterized the spiking responses of the pentascolopidial chordotonal organ of 20 Drosophila larvae to mechanical stimuli and reveal a clear role in proprioception.

neuroscience↗

bioRxiv2022

Metabolism is correlative not causative for age-related auditory decline in an insect model

Aging is due to a complex decline of multiple biological processes. Some of the causes include oxidative damage, mitochondrial and proteostatic dysfunction, and DNA damage. The result is that as biological systems age their performance deteriorates. This age-related decline is well quantified, and experienced, for human hearing and is presumed to be due to a decrease in the ears metabolism - specifically a decrease in ability to maintain an electrochemical gradient, the endocochlear potential. However, direct measurements of metabolism across a lifespan in an auditory system are lacking. Even if metabolism does decrease with age, the question remains is it a cause of age-related auditory decline or simply correlative? All auditory systems across the animal kingdom share functional principles including ion pumping cells, auditory receptors, spiking auditory nerves and multiple supporting cells. Therefore, we used an insect, the desert locust, Schistocerca gregaria, as a physiologically versatile model to understand how cellular metabolism correlates with age and impacts on age-related auditory decline. We found that although metabolism correlates with age-related auditory decline it is not causative.

neuroscience↗

bioRxiv2022

Labeled lines for fat and sugar reward combine to promote overeating

Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits are poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for detection of dietary fats and sugars. Using activity-dependent genetic capture of nutrient-specific vagal neurons activated in response gut infusions, we demonstrate the existence of separate hard-wired reward circuits for fat and sugar that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases overeating compared to fat or sugar alone. This work provides new insight on the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.

neuroscience↗

bioRxiv2021

Physiological changes throughout the ear due to age and noise - a longitudinal study

Biological and mechanical systems, whether by their overuse or their aging, will inevitably fail. Hearing provides a poignant example of this with noise-induced and age-related hearing loss. Hearing loss is not unique to humans, however, and is experienced by all animals in the face of wild and eclectic differences in ear morphology and operation. Here we exploited the high throughput and accessible tympanal ear of the desert locust, Schistocerca gregaria (mixed sex) to rigorously quantify changes in the auditory system due to noise exposure (3 kHz pure tone at 126 dB SPL) and age. We analysed tympanal dispalcements, morphology of the auditory Mullers organ and measured activity of the auditory nerve, the transduction current and electrophysiological properties of individual auditory receptors. We found that noise mildly and transiently changes tympanal displacements, decreases both the width of the auditory nerve and the transduction current recorded from individual auditory neurons. Whereas age - but not noise - decreases the number of auditory neurons and increases their resting potential. Multiple other properties of Mullers organ were unaffected by either age or noise including: the number of supporting cells in Mullers organ or the nerve, membrane resistance and capacitance of the auditory neurons. The sound-evoked activity of the auditory nerve decreased as a function of age and this decrease was exacerbated by noise, with the largest difference during the middle of their life span. This middle-aged deafness pattern of hearing loss mirrors that found for humans exposed to noise early in their life. Key point summaryO_LIAge and noise lead to hearing loss. C_LIO_LITympanal displacements have a transient and delayed reduction after noise. C_LIO_LIThe number of auditory neurons decreases with age. The width of the auditory nerve is reduced with noise exposure. C_LIO_LILocusts repeatedly exposed to noise lost their hearing compared to silent controls, but their hearing became similar to old silent control locusts due to age-related hearing loss dominating. C_LIO_LIThe electrophysiological properties of the auditory neurons and the transduction current remained unchanged for aged locusts but repeated noise exposure led to a cumulative decrease in the transduction current. C_LI

physiology↗

bioRxiv2019

Physiological Basis of noise-induced hearing loss in a tympanal ear

Acoustic overexposure, such as listening to music too loud and too often, results in noise-induced hearing loss. The pathologies of this prevalent sensory disorder begin in the synapses of the primary auditory receptors, their postsynaptic partners and supporting cells. The extent of noise-induced damage, however, is determined by over-stimulation of primary auditory receptors. When over-stimulated, an excessive amount of positive ions flood into the primary auditory receptors, triggering the activation of ion channels and possibly disrupting their ability to encode sound. A systematic characterisation of the electrophysiological function of primary auditory receptors is warranted to understand how noise-exposure impacts on downstream targets, where the pathologies of hearing loss begin. Here, we used the experimentally-accessible locust ear to characterise noise-induced changes in the auditory receptors. Although, we found a decrease in ability of the primary auditory neurons to encode sound, this is probably due to pathologies of their supporting cells.

neuroscience↗