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Nature Communications · 2023
Identifiziert Octopamin als zentralen Modulator des Hörens von Malariamücken und als mögliches Insektizid-Ziel.
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iScience · 2021
Zeigt den schnellen Umsatz und die aktivitätsabhängige transkriptionelle Kontrolle des NompC-Mechanotransduktors.
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Scientific Reports · 2020
Kartiert das Hören über den Lebensverlauf der Fliege und identifiziert konservierte Regulatoren auditiver Homöostase und Alterung.
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2025 · iScience
This publication investigates Using a female-specific isoform of doublesex to explore male-specific hearing in mosquitoes.
2025 · iScience
This publication investigates The GABA(A) receptor RDL modulates the auditory sensitivity of malaria mosquitoes.
2025 · bioRxiv
Abstract Hearing begins when ears convert sound into neuronal excitation. The hearing organs of male Anopheles mosquitoes rank amongst the most sensitive ears evolved. Males use them to detect faint female flight tones within noisy mating swarms, but female flight tones largely lie above the male’s hearing range. We report a mechanism by which inaudible higher-frequency primary tones become audible through intrinsically generated, lower-frequency distortion tones. Distortion-evoked responses show ∼10-times greater sensitivity and 45% higher temporal precision than those of same-frequency primary tones. Moreover, self-sustained oscillations of the male’s ear dramatically reshape auditory frequency tuning and neuronal recruitment. By one mechanism, mosquito ears thus create audible signals and isolate these from the most salient frequencies of background noise. In audiology, distortions are used for diagnostics; their biological relevance, however, is unknown. Our results suggest that distortions are not mere by-products of the auditory process, but integral to its signaling logic.
2025 · Proceedings of the National Academy of Sciences
Distortion products are tones produced through nonlinear effects of a system simultaneously detecting two or more frequencies. These combination tones are ubiquitous to vertebrate auditory systems and are generally regarded as byproducts of nonlinear signal amplification. It has previously been shown that several species of infectious-disease-carrying mosquitoes utilize these distortion products for detecting and locating potential mates. Furthermore, the mechanical tuning curve of the male mosquito flagellum was shown not to be aligned with that of its sensory neural elements. Using a generic theoretical model for acoustic sensing, we evaluate the signal-detection advantages and disadvantages that are implied by these two schemes: distortion product detection and cascading a signal through multiple layers of oscillator elements of different characteristic frequency. Last, we show that the combination of these two schemes yields a signal detector with enhanced frequency selectivity and speed of response, thus enabling the detection of transient, narrowband flight tones.
2024 · Hearing Research
This publication investigates A burden shared: The evolutionary case for studying human deafness in Drosophila.
2023 · bioRxiv
Despite the artificial conditions, flight tone recordings taken from tethered mosquitoes can provide valuable information on the acoustic signals produced by male and female mosquitoes. Although auditory responsiveness appears to be largely (and possibly exclusively) restricted to males, the flight tones of both sexes have sensory-ecological relevance, as it is the mixing of the two tones that produces audibility in males and thereby facilitates reproduction. This protocol describes how to record wing flapping from mounted mosquitoes and how to estimate wingbeat frequencies from those recordings.
2023 · bioRxiv
Phonotaxis experiments can provide information on the spectrum of sounds relevant to mosquito acoustic behaviors. It is widely known that males of disease-transmitting species are attracted to tones with frequencies resembling the wingbeat frequencies of their conspecific females. Thus, phonotaxis experiments can be coupled with wingbeat frequency measurements to inform the development of vector control tools such as acoustic traps and lures. This protocol describes how to set up and execute a phonotaxis experiment.
2023 · bioRxiv
Immunohistochemistry has played a major role in improving our understanding of the anatomy and function of the nervous system. The use of fluorescent dyes that label different antigens reveals how biological tissues are built and how interactions between cells take place. Obtaining this information is particularly important in the case of the mosquito ear given its highly complex anatomy. This protocol describes an immunohistochemical technique to stain the mosquito ear. The first steps of the procedure include the embedding of the tissue in albumin-gelatin and its sectioning into thin slices to allow antibody penetration. The immunohistochemical procedure can be exploited to detect protein expression and localization by using antibodies specifically raised against the protein of interest or that recognize epitope tags fused to proteins using genome editing methods.
2023 · Nature Communications
Abstract Malaria mosquitoes acoustically detect their mating partners within large swarms that form transiently at dusk. Indeed, male malaria mosquitoes preferably respond to female flight tones during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing in the species Anopheles gambiae . Among them, octopamine stands out as an auditory modulator during swarm time. In-depth analysis of octopamine auditory function shows that it affects the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and controls the erection of antennal fibrillae. We show that two α- and β-adrenergic-like octopamine receptors drive octopamine’s auditory roles and demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings highlight octopamine as key for mosquito hearing and mating partner detection and as a potential novel target for mosquito control.
2023 · bioRxiv
Electrophysiological recordings taken from the antennal nerve can provide essential information on the general auditory condition of the mosquito tested. Furthermore, electrophysiological recordings provide detailed information on what types of stimulation induce the largest nerve responses. When these are used in conjunction with a vibrometer to measure the corresponding movement of the antennal ear during stimulation, a comprehensive overview of hearing function can be obtained. This protocol can be applied to male and female adults from any mosquito strain and can be scaled relative to available resources.
2023 · bioRxiv
The acoustic physiology of mosquitoes is perhaps the most complex within the entire insect class. Past research has uncovered several of its—sometimes stunningly unconventional—principles, but many mysteries remain. Their solution necessitates a concerted transdisciplinary effort to successfully link the neuroanatomical and biophysical properties of mosquito flagellar ears to the behavioral ecology of entire mosquito populations. Neuroanatomically, mosquito ears can rival those of humans in both complexity and sheer size. The approximately 16,000 auditory hair cells within the human organ of Corti, for example, are matched by the approximately 16,000 auditory neurons in the Johnston's organ of a male Anopheles mosquito. Both human and mosquito ears receive very extensive efferent innervation, which modulates their function in ways that are as yet poorly understood. Different populations of neuronal and nonneuronal cell types divide the labor of the mosquito ear amongst themselves. Yet, what exactly this labor is, and how it is achieved, is at best vaguely known. For the majority of mosquitoes, biologically relevant sounds are inextricably linked to their flight tones. Either these flight tones are (directly) the sounds of interest or they contribute (indirectly) to the production of audible sound through a process called nonlinear distortion. Finally, male ears can generate tones themselves: The generation of an internal “phantom copy” of a female flight tone (or self-sustained oscillation ) is believed to aid the male hearing process. Here, we introduce protocols that target the mosquitoes’ auditory neuroanatomy, electrophysiology, and behavior to help shed light on some of these issues.
2022 · Science Advances
By beating their wings faster around sunset, male Anopheles mosquitoes sensitize their auditory system to female flight tones.
2022 · bioRxiv
Hearing is an essential sense in the life cycle of malaria mosquitoes. Within large swarms formed transiently at dusk, mosquitoes acoustically recognize their mating partners by their wingbeats. Indeed, malaria mosquitoes only respond to the flight tones of mating partners during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are still largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing. Among them, octopamine stands out as regulator of the auditory performance during swarm time. To explore octopamine roles in mosquito hearing, we carried out an in-depth analysis of octopamine-mediated effects on auditory function. We found that octopamine affects the properties of the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and it controls the erection of antennal fibrillae in males. We found that two different receptors are driving octopamine auditory roles, including a novel beta octopamine receptor. We also demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings identify octopamine signalling as a key component of hearing and mating partner detection in malaria mosquitoes, and as a potential novel target for mosquito control.
2022 · Frontiers in Cell and Developmental Biology
Meniere’s disease (MD) is an inner ear disorder characterised by recurrent vertigo attacks associated with sensorineural hearing loss and tinnitus. Evidence from epidemiology and Whole Exome Sequencing (WES) suggests a genetic susceptibility involving multiple genes, including α-Dystrobrevin ( DTNA ). Here we investigate a Drosophila model. We show that mutation, or knockdown, of the DTNA orthologue in Drosophila , Dystrobrevin ( Dyb ), results in defective proprioception and impaired function of Johnston’s Organ (JO), the fly’s equivalent of the inner ear. Dyb and another component of the dystrophin-glycoprotein complex (DGC), Dystrophin ( Dys ), are expressed in support cells within JO. Their specific locations suggest that they form part of support cell contacts, thereby helping to maintain the integrity of the hemolymph-neuron diffusion barrier, which is equivalent to a blood-brain barrier. These results have important implications for the human condition, and notably, we note that DTNA is expressed in equivalent cells of the mammalian inner ear.
2021 · iScience
This publication investigates Turnover and activity-dependent transcriptional control of NompC in the Drosophila ear.
2021 · bioRxiv
Abstract Mating swarms of malaria mosquitoes form every day at sunset throughout the tropical world, they typically last less than 30 minutes. Activity patterns must thus be highly synchronized between the sexes. Moreover, males must be able to identify the few sporadically entering females by detecting the females’ faint flight tones. We here show that the Anopheles circadian clock ensures a tight synchrony of male and female activity and –importantly – also retunes the males’ acoustic detection system: by lifting their own flight tones at dusk, males actively enhance the audibility of females. The reported phenomenon of ‘harmonic convergence’ is a random by-product of the mosquitoes’ flight tone variance. Intriguingly, flight tones of individual mosquitoes occupy narrow –partly non-overlapping-frequency ranges, suggesting that the audibility of individual females varies across males. One Sentence Summary Male mosquitoes sharpen their hearing at sunset.
2020 · Scientific Reports
Abstract Age-related hearing loss (ARHL) is a threat to future human wellbeing. Multiple factors contributing to the terminal auditory decline have been identified; but a unified understanding of ARHL - or the homeostatic maintenance of hearing before its breakdown - is missing. We here present an in-depth analysis of homeostasis and ageing in the antennal ears of the fruit fly Drosophila melanogaster . We show that Drosophila , just like humans, display ARHL. By focusing on the phase of dynamic stability prior to the eventual hearing loss we discovered a set of evolutionarily conserved homeostasis genes. The transcription factors Onecut (closest human orthologues: ONECUT2, ONECUT3), Optix (SIX3, SIX6), Worniu (SNAI2) and Amos (ATOH1, ATOH7, ATOH8, NEUROD1) emerged as key regulators, acting upstream of core components of the fly’s molecular machinery for auditory transduction and amplification. Adult-specific manipulation of homeostatic regulators in the fly’s auditory neurons accelerated - or protected against - ARHL.
2020 · Current Opinion in Insect Science
This publication investigates Buzzkill: targeting the mosquito auditory system.
2020 · Parasites & Vectors
Abstract Background Release of gene-drive mutants to suppress Anopheles mosquito reproduction is a promising method of malaria control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. At a behavioural level, gene-drive carrying mutants should be at least as sexually attractive as the wildtype populations they compete against, with a key element of Anopheles copulation being acoustic courtship. We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae ( s.l. ) cages. Methods Anopheles rely on flight tones produced by the beating of their wings for acoustic mating communication. We assessed the impact of disrupting a female-specific isoform of the doublesex gene ( dsxF ) on the wing beat frequency (WBF; measured as flight tone ) of males (XY) and females (XX) in homozygous dsxF − mutants ( dsxF −/− ), heterozygous dsxF − carriers ( dsxF +/− ) and G3 dsxF + controls ( dsxF + / + ). To exclude non-genetic influences, we controlled for temperature and wing length. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes. Results A previous study showed an altered phenotype only for dsxF −/− females, who appear intersex, suggesting that the female-specific dsxF allele is haplosufficient. We identified significant, dose-dependent increases in the WBF of both dsxF −/− and dsxF +/− females compared to dsxF + / + females. All female WBFs remained significantly lower than male equivalents, though. Males showed stronger phonotactic responses to the WBFs of control dsxF + / + females than to those of dsxF +/− and dsxF −/− females. We found no evidence of phonotaxis in any female genotype. No male genotypes displayed any deviations from controls. Conclusions A prerequisite for anopheline copulation is the phonotactic attraction of males towards female flight tones within mating swarms. Reductions in mutant acoustic attractiveness diminish their mating efficiency and thus the efficacy of population control efforts. Caged population assessments may not successfully reproduce natural mating scenarios. We propose to amend existing testing protocols to better reflect competition between mutants and target populations. Our findings confirm that dsxF disruption has no effect on males; for some phenotypic traits, such as female WBFs, the effects of dsxF appear dose-dependent rather than haplosufficient.
2018 · Nature Communications
Abstract Hearing is essential for the courtship of one of the major carriers of human disease, the mosquito. Males locate females through flight-tone recognition and both sexes engage in mid-air acoustic communications, which can take place within swarms containing thousands of individuals. Despite the importance of hearing for mosquitoes, its mechanisms are still largely unclear. We here report a multilevel analysis of auditory function across three disease-transmitting mosquitoes ( Aedes aegypti , Anopheles gambiae and Culex quinquefasciatus ). All ears tested display transduction-dependent power gain. Quantitative analyses of mechanotransducer function reveal sex-specific and species-specific variations, including male-specific, highly sensitive transducer populations. Systemic blocks of neurotransmission result in large-amplitude oscillations only in male flagellar receivers, indicating sexually dimorphic auditory gain control mechanisms. Our findings identify modifications of auditory function as a key feature in mosquito evolution. We propose that intra-swarm communication has been a driving force behind the observed sex-specific and species-specific diversity.
2018 · Frontiers in Behavioral Neuroscience
This publication investigates How Many Clocks, How Many Times? On the Sensory Basis and Computational Challenges of Circadian Systems.
2017 · Journal of Biological Rhythms
In Drosophila, as in other animals, the circadian clock is a singular entity in name and concept only. In reality, clock functions emerge from multiple processes and anatomical substrates. One distinction has conventionally been made between a central clock (in the brain) and peripheral clocks (e.g., in the gut and the eyes). Both types of clock generate robust circadian oscillations, which do not require external input. Furthermore, the phases of these oscillations remain exquisitely sensitive to specific environmental cues, such as the daily changes of light and temperature. When these cues conflict with one another, the central clock displays complex forms of sensory integration; how peripheral clocks respond to conflicting input is unclear. We therefore explored the effects of light and temperature misalignments on peripheral clocks. We show that under conflict, peripheral clocks preferentially synchronize to the light stimulus. This photic dominance requires the presence of the circadian photoreceptor, Cryptochrome.
2017 · eLife
Animals are characterized by a set of highly conserved developmental regulators. Changes in the cis-regulatory elements of these regulators are thought to constitute the major driver of morphological evolution. However, the role of coding sequence evolution remains unresolved. To address this question, we used the Atonal family of proneural transcription factors as a model. Drosophila atonal coding sequence was endogenously replaced with that of atonal homologues (ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral proneural genes. ATHs and the ancestral-like coding sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATH factors displayed different levels of proneural activity as reflected by the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that coding sequence evolution can underlie quantitative variation in sensory development and function.
2016 · Cell Reports
This publication investigates Sensory Conflict Disrupts Activity of the Drosophila Circadian Network.
2016 · Current Biology
This publication investigates Comparative Aspects of Hearing in Vertebrates and Insects with Antennal Ears.
2015 · Journal of Comparative Physiology A
This publication investigates Prestin is an anion transporter dispensable for mechanical feedback amplification in Drosophila hearing.
2015 · Current Opinion in Neurobiology
This publication investigates Hearing in Drosophila.
2014 · Science
Coordinating the Clock In flies, the mechanosensory chordotonal organs help to coordinate the effects of temperature on circadian cycles. Simoni et al. (p. 525 ) provide a mechanism by which mechanosensory input is processed to help to synchronize the biological clock in Drosophila melanogaster . The chordotonal organs, which have similarities to the mammalian ear, were also required for sensation of a vibration stimulus and its effects on the endogenous brain clock. The chordotonal organs, present in the joints of the limbs, provide neuronal signals that allow the animal to sense its position or posture—and thus might mediate feedback of a range of behaviors onto the endogenous biological clock.
2013 · Current Biology
This publication investigates Sensory transduction: confusing the senses.
2012 · Nature Neuroscience
This publication investigates Direct gating and mechanical integrity of Drosophila auditory transducers require TRPN1.
2011 · Current Biology
This publication investigates Active process mediates species-specific tuning of Drosophila ears.
2010 · European Journal of Neuroscience
Abstract Vertebrate inner‐ear hair cells use mechanical feedback to amplify sound‐induced vibrations. The gain of this ‘cochlear amplifier’ is centrally controlled via efferent fibres that, making synaptic contacts with the hair cells, modulate the feedback gain. The sensory neurons of the Drosophila ear likewise employ mechanical feedback to assist sound‐evoked vibrations, yet whether this neuron‐based feedback is also subject to efferent control has remained uncertain. We show here that the function of Drosophila auditory neurons is independent of efferent modulation, and that no synaptic transmission is needed to control the gain of mechanical feedback amplification. Immunohistochemical, mechanical and electrophysiological analyses revealed that the Drosophila auditory organ lacks peripheral synapses and efferent innervations, and that blocking synaptic transmission in a pan‐neural manner does not affect the afferent electrical activity of the sensory neurons or the mechanical feedback gain. Hence, unlike the cochlear amplifier of vertebrates, mechanical feedback amplification in Drosophila is not associated with an efferent control system but seems to be a purely local process that is solely controlled peripherally within the ear itself.
2010 · Nature Communications
This publication investigates A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia.
2009 · Neuron
This publication investigates Temperature entrainment of Drosophila's circadian clock involves the gene nocte and signaling from peripheral sensory tissues to the brain.
2008 · Current Biology
This publication investigates Transducer-based force generation explains active process in Drosophila hearing.
2007 · Current Biology
This publication investigates Mechanical signatures of transducer gating in the Drosophila ear.
2007 · Fly
This publication investigates Drosophila mechanotransduction--linking proteins and functions.
2006 · Nature Neuroscience
This publication investigates Specification of auditory sensitivity by Drosophila TRP channels.
2005 · Proceedings of the National Academy of Sciences
In insects and vertebrates alike, hearing is assisted by the motility of mechanosensory cells. Much like pushing a swing augments its swing, this cellular motility is thought to actively augment vibrations inside the ear, thus amplifying the ear's mechanical input. Power gain is the hallmark of such active amplification, yet whether and how much energy motile mechanosensory cells contribute within intact auditory systems has remained uncertain. Here, we assess the mechanical energy provided by motile mechanosensory neurons in the antennal hearing organs of Drosophila melanogaster by analyzing the fluctuations of the sound receiver to which these neurons connect. By using dead WT flies and live mutants ( tilB 2 , btv 5P1 , and nompA 2 ) with defective neurons as a background, we show that the intact, motile neurons do exhibit power gain. In WT flies, the neurons lift the receiver's mean total energy by 19 zJ, which corresponds to 4.6 times the energy of the receiver's Brownian motion. Larger energy contributions (200 zJ) associate with self-sustained oscillations, suggesting that the neurons adjust their energy expenditure to optimize the receiver's sensitivity to sound. We conclude that motile mechanosensory cells provide active amplification; in Drosophila , mechanical energy contributed by these cells boosts the vibrations that enter the ear.
2026 · Frontiers in Neurology
Background Severe traumatic brain injury (sTBI) often results in prolonged coma and significant long-term disability. Evidence-based, widely accessible approaches to accelerate recovery of consciousness remain limited. This study evaluated whether adding a combined regimen of hyperbaric oxygen therapy (HBOT) and systematic auditory stimulation (SAS) to standard neurosurgical care improves recovery of consciousness and short-term outcomes in comatose patients with sTBI. Methods In this prospective randomized controlled trial, 89 comatose patients with sTBI [Glasgow Coma Scale (GCS) < 8] were randomized to standard neurosurgical care (control, n = 44) or standard care in addition to HBOT and SAS (HBOT+SAS, n = 45). HBOT was delivered at a pressure of 2.0 atmospheres absolute (ATA) for 60 min/session, five sessions per week for 4 weeks. SAS consisted of structured family-delivered storytelling and music sessions three times daily following a predefined schedule. The primary outcome was the change in the Full Outline of UnResponsiveness (FOUR) score from baseline to Day 28. Secondary outcomes included the GCS and Coma Recovery Scale-Revised (CRS-R) scores, the Glasgow Outcome Scale (GOS) score at 3 months, and serum biomarkers [such as S100B, neuron-specific enolase (NSE), and brain-derived neurotrophic factor (BDNF)]; care-related satisfaction was analyzed as an exploratory outcome. Secondary endpoints were interpreted using a prespecified Bonferroni-adjusted threshold ( p < 0.01). Results Compared to the control group, the HBOT+SAS group demonstrated greater improvement in measures of consciousness at Day 28 (FOUR: 12.1 ± 2.4 vs. 9.3 ± 2.1; GCS: 11.3 ± 2.2 vs. 9.1 ± 1.9; CRS-R: 11.8 ± 2.3 vs. 8.1 ± 2.0; all p < 0.001). At 3 months, the functional outcome was higher in the HBOT+SAS group (GOS: 4.3 ± 0.5 vs. 3.6 ± 0.6, p < 0.001). Biomarker patterns indicated a reduction in neuronal injury and an enhancement in neurotrophic activity. Specifically, levels of S100B and NSE were lower in the HBOT+SAS group (both p < 0.001), and BDNF was higher ( p = 0.003) in this group. No serious adverse events related to the intervention were reported. Satisfaction outcomes favored HBOT+SAS (88.89% vs. 59.09%, p = 0.005) and were interpreted as exploratory due to the unblinded design of the study. Conclusion The addition of HBOT+SAS to standard care was associated with improved recovery of consciousness and better 3-month functional outcomes in comatose patients with sTBI, supported by consistent findings from clinical scales and serum biomarkers. However, since the trial did not include HBOT-only or SAS-only comparator arms, the findings support the effectiveness of the combined regimen compared to standard care but do not determine whether HBOT and SAS have a synergistic effect.
2026 · Publication
ABSTRACT Macroautophagy, a catabolic process conserved across evolution, participates in fundamental aspects of synaptic function and neuronal survival. Exosomes are extracellular vesicles that mediate cell communication, including emerging roles mediating brain intercellular signaling, synaptic function and neuronal survival. Indeed, both autophagy and exosome release interact with each other, but this interplay is poorly characterized at the neuronal synapse, especially in the context of neurodegenerative diseases. Here, we report that at the presynaptic compartment the autophagy protein Atg18a/WIPI2 regulates exosome release at the level of the multivesicular body. The Parkinson disease mutation R258Q in the protein Synaptojanin inhibits synaptic autophagy, and causes locomotion deficits, seizures and neurodegeneration. We found that this mutation also reduces exosome release and that the dopaminergic overexpression of Atg18a in Synaptojanin mutant animals restores exosome release, locomotion and dopaminergic survival without restoring synaptic autophagy. Our data reports a novel function of Atg18a in the regulation of exosome release and spotlights the role of exosome release in the pathogenesis of Parkinson disease.
2026 · Current Biology
This publication investigates Myosin II-driven contractions of supporting cap cells promote sensory adaptation of Drosophila proprioceptors.
2026 · Developmental Psychobiology
ABSTRACT Infant face recognition shows plasticity, with recent evidence indicating enhancement by the presence of emotional facial expressions. The mechanisms and domain‐generality of this effect remain largely unknown. This study tested whether auditory emotional cues (vocalizations) facilitated infants' recognition of other‐race faces, a perceptual challenge during the first year of life. Infants ( N = 89) were presented with emotionally neutral faces paired with happy, sad, or neutral vocal sounds in a within‐subjects design. Experiment 1 assessed recognition using identical face images between the familiarization and test phases, while Experiment 2 examined face recognition across viewpoint changes. Across both experiments, infants exhibited successful face recognition only when they were learned with emotional sounds (happy and sad). This facilitative effect remained stable across the tested age range and did not differ between happy and sad vocalizations. Infants' eye movement data revealed comparable face‐looking patterns across conditions, suggesting that the facilitation was not driven by changes in visual attention. Thus, incidental, cross‐modal emotional signals significantly enhance infant face recognition. This underscores the early integrative nature of emotion processing and its catalytic role in cognitive development.
2026 · eLife
Age-related hearing loss is a complex phenomenon. The earliest-onset degenerative event is the gradual loss of neural connections between the cochlea and auditory brainstem. To probe for perceptual deficits that might arise from this loss, cochlear synaptopathy was induced pharmacologically in young-adult gerbils, which were then tested in a challenging listening task for the perception of temporal fine structure. Treated gerbils behaved no differently than normal-hearing, young-adult animals. In contrast, old gerbils, which typically express many cochlear and central-neural pathologies, showed impaired perception. To probe for the underlying mechanisms, single-unit responses were obtained from the auditory nerve to the same test stimuli. Responses from old gerbils showed no impairment in temporal locking to the stimulus fine structure. However, responses were significantly more driven by slower temporal fluctuations of the stimulus envelope, suggesting that the central auditory system may be unable to extract the relevant information for discrimination from such altered inputs.
2025 · bioRxiv
Abstract Exposure to loud sounds can lead to hearing impairments. Speech comprehension, especially in the presence of background sounds, allegedly declines as a consequence of noise-induced hearing loss. However, the connection between noise overexposure and deteriorated speech-in-noise perception is not clear yet and potential underlying mechanisms are still under debate. This study investigates speech-in-noise discrimination in young-adult Mongolian gerbils before and after an acoustic trauma to reveal possible noise-induced changes in the perception of speech sounds and to examine the commonly suggested link between noise exposure and speech-in-noise perception difficulties. Nine young-adult gerbils were trained to discriminate a deviant consonant-vowel-consonant combination (CVC) or vowel-consonant-vowel combination (VCV) in a sequence of CVC or VCV standards, respectively. The logatomes were spoken by different speakers and masked by a steady-state speech-shaped noise. After the gerbils completed the behavioral baseline experiments, they underwent an acoustic trauma and collected data for the second time in the behavioral experiments. Applying multidimensional scaling, response latencies were used to generate perceptual maps reflecting the gerbils’ internal representations of the sounds pre- and post-trauma. To evaluate how the discrimination of vowels and consonants was altered after the acoustic trauma, changes in response latencies between phoneme pairs were investigated with regard to their articulatory features. Auditory brainstem responses were measured to assess peripheral auditory function. We found that the perceptual maps of vowels and consonants were very similar before and after noise exposure. Interestingly, the gerbils’ overall vowel discrimination ability was improved after the acoustic trauma, even though the gerbils suffered from noise-induced hearing loss. In contrast to the improvements in vowel discrimination, there were only minor changes in the gerbils’ ability to discriminate consonants. Moreover, the noise exposure showed a differential influence on the response latencies for vowel and consonant discriminations depending on the articulatory features of the specific phonemes.
2025 · Nature Neuroscience
This publication investigates NOMPC ion channel hinge forms a gating spring that initiates mechanosensation.
2025 · Aging Cell
ABSTRACT Invertebrate models have been instrumental in advancing our understanding of the molecular mechanisms of ageing. The isolation of single gene mutations that both extend lifespan and improve age‐related health have identified potential targets for therapeutic intervention to alleviate age‐related morbidity. Here, we find that genetic loss of function of the G protein‐coupled metabotropic glutamate receptor (DmGluRA) in Drosophila extends the lifespan of female flies. This longevity phenotype was accompanied by lower basal levels of oxidative stress and improved stress tolerance, and differences in early‐life behavioural markers. Gene expression changes in DmGluRA mutants identified reduced ribosome biogenesis, a hallmark of longevity, as a key process altered in these animals. We further show that the pro‐longevity effects of reduced DmGluRA signalling are dependent on the fly homologue of Fragile X Mental Retardation Protein (FMRP), an important regulator of ribosomal protein translation. Importantly, we can recapitulate lifespan extension using a specific pharmacological inhibitor of mGluR activity. Hence, our study identifies metabotropic glutamate receptors as potential targets for age‐related therapeutics.
2024 · bioRxiv
Abstract Many elderly listeners have difficulties with speech-in-noise perception, even if auditory thresholds in quiet are normal. The mechanisms underlying this compromised speech perception with age are still not understood. For identifying the physiological causes of these age-related speech perception difficulties, an appropriate animal model is needed enabling the use of invasive methods. In a comparative behavioral study, we used young-adult and quiet-aged Mongolian gerbils as well as young and elderly human subjects to investigate the age-related changes in speech-in-noise perception evaluating whether gerbils are an appropriate animal model for the age-related decline in speech-in-noise processing of human listeners. Gerbils and human subjects had to report a deviant consonant-vowel-consonant combination (CVC) or vowel-consonant-vowel combination (VCV) in a sequence of CVC or VCV standards, respectively. The logatomes were spoken by different speakers and masked by a steady-state speech-shaped noise. Response latencies were measured to generate perceptual maps employing multidimensional scaling, visualizing the subjects’ internal representation of the sounds. By analyzing response latencies for different types of vowels and consonants, we investigated whether aging had similar effects on speech-in-noise perception in gerbils compared to humans. For evaluating peripheral auditory function, auditory brainstem responses and audiograms were measured in gerbils and human subjects, respectively. We found that the overall phoneme discriminability in gerbils was independent of age, whereas consonant discriminability was declined in humans with age. Response latencies were generally longer in aged than in young gerbils and humans, respectively. Response latency patterns for the discrimination of different vowel or consonant types were different between species, but both gerbils and humans made use of the same articulatory features for phoneme discrimination. The species-specific response latency patterns were mostly unaffected by age across vowel types, while there were differential aging effects on the species-specific response latency patterns of different consonant types.
2024 · The Laryngoscope
Objective Middle ear surgery involves reconstruction of the ossicular chain, predominately using rigid implants. New middle ear prostheses strive to mimic the physiologic micromovements of the ossicular chain and prevent dislocation, protrusion, and preloading of the annular ligament due to pressure fluctuations. Methods Thirty‐five patients were included in a monocentric, prospective observational study. Patients received tympanoplasty with ossicular reconstruction using the mCLIP ARC partial prosthesis. This titanium prosthesis is equipped with a clip mechanism for coupling at the stapes and a ball joint connecting headplate and shaft. At short‐term (ST) and mid‐term (MT) follow‐up, pure‐tone audiometry was performed and the pure tone average of 0.5, 1, 2, and 3 kHz (PTA4) was calculated. The audiological outcome was compared with retrospective data of the Dresden titanium clip prosthesis. Results The new prosthesis shows favorable clinical results. Pure‐tone audiometry showed satisfactory results in ST and MT follow‐up, with the PTA4 air‐bone gap (ABG) decreasing from 24.5 (±11) dB to 17.4 (±7.9) dB at the ST follow‐up at 27 days to 15.6 (±10.3) dB at MT follow‐up at 196 days ( n = 32). A PTA4‐ABG value of less than 20 dB was achieved by 63% of patients at ST follow‐up and by 77% at MT follow‐up. There was no significant difference in PTA4 ABG compared to the Dresden titanium clip prosthesis during ST follow‐up ( p = 0.18). Conclusion The mCLIP ARC partial prosthesis, a new middle ear prosthesis with a balanced ball joint, shows promising audiological results and is a safe and effective choice for patients with chronic ear disease. Level of Evidence 3 Laryngoscope , 134:3323–3328, 2024
2024 · Laryngo-Rhino-Otologie
This publication investigates Der partielle Ossikelersatz mit einer neuen Kugelgelenksprothese – die mCLIP ARC Prothese.
2024 · Laryngo-Rhino-Otologie
This publication investigates Cell membrane manipulations affect mechano-electrical transduction currents in rat auditory hair cells.
2024 · bioRxiv
Abstract Age-related hearing loss is a complex phenomenon. The earliest-onset degenerative event is the gradual loss of neural connections between cochlea and auditory brainstem. To probe for perceptual deficits that might arise from this loss, cochlear synaptopathy was induced pharmacologically in young-adult gerbils, which were then tested in a challenging listening task for the perception of temporal fine structure. Treated gerbils behaved no differently than normal-hearing, young-adult animals. In contrast, old gerbils, which typically express many cochlear and central-neural pathologies, showed impaired perception. To probe for the underlying mechanisms, single-unit responses were obtained from the auditory nerve to the same test stimuli. Responses from old gerbils showed no impairment in temporal locking to the stimulus fine structure. However, responses were significantly more driven by slower temporal fluctuations of the stimulus envelope, suggesting that the central auditory system may be unable to extract the relevant information for discrimination from such altered inputs.
2024 · The Journal of Neuroscience
Pure-tone audiograms often poorly predict elderly humans’ ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with “virtual headphones”, recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron-emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors. Significance statement Older people often have difficulty communicating in everyday situations involving multiple speakers and other sound sources. Binaural processing facilitates hearing in such complex listening situations. Peripheral damage, such as synapse loss in the inner ear, is thought to be an important factor contributing to these difficulties. However, the role of central processing deficits has received less attention. Here, we investigate age-related binaural processing in Mongolian gerbils using brainstem responses, midbrain single-unit responses, positron emission tomography, and reward-based animal psychophysics. Behavioral deficits in binaural processing precede increases in audiometric threshold, as do changes in central inhibition and physiological binaural processing. Synapse loss in cochlear regions tuned to the stimulus frequency, however, does not change and therefore unlikely contributes to age-related binaural deficits.
2024 · Hearing Research
This publication investigates A burden shared: The evolutionary case for studying human deafness in Drosophila.
2023 · bioRxiv
Abstract Synapses are specialized neuronal compartments essential for brain communication. Neuronal communication mostly relies on the adequate supply and renovation of synaptic vesicles that fuse with the plasma membrane and release neurotransmitters in response to action potentials. Autophagy is an evolutionary conserved cellular mechanism essential for homeostasis that can be locally regulated in the neuronal synapse. However, the precise mechanisms controlling synaptic autophagy, especially during neuronal communication and pathological scenarios, remain elusive. Here, we report that neuronal activity and amino-acid deprivation regulate synaptic autophagy via distinct molecular mechanisms. We show that Synaptogyrin, a highly abundant presynaptic protein found in synaptic vesicles, is a novel negative regulator of synaptic autophagy in response to neuronal activity without affecting autophagy induction via amino-acid deprivation. We demonstrate that loss of Synaptogyrin modifies the localization of the autophagy protein Atg9 and boosts autophagosome formation at the synapse. Furthermore, activation of synaptic autophagy by loss of Synaptogyrin, but not by amino-acid deprivation, leads to the degradation of synaptic vesicle components via autophagy. Reducing the levels of Synaptogyrin results in the degradation of synaptic Tau via autophagy and restores autophagy dysfunction observed in a Drosophila Tau model of Frontotemporal Dementia (FTD). Our data provide novel and valuable information to understand how autophagy is regulated at the synapse in response to neuronal activity and how this process participates in neuronal (dys)function.
2023 · The Journal of the Acoustical Society of America
Masking can reduce the efficiency of communication and prey and predator detection. Most underwater sounds fluctuate in amplitude, which may influence the amount of masking experienced by marine mammals. The hearing thresholds of two harbor seals for tonal sweeps (centered at 4 and 32 kHz) masked by sinusoidal amplitude modulated (SAM) Gaussian one-third octave noise bands centered around the narrow-band test sweep frequencies, were studied with a psychoacoustic technique. Masking was assessed in relation to signal duration, (500, 1000, and 2000 ms) and masker level, at eight amplitude modulation rates (1–90 Hz). Masking release (MR) due to SAM compared thresholds in modulated and unmodulated maskers. Unmodulated maskers resulted in critical ratios of 21 dB at 4 kHz and 31 dB at 32 kHz. Masked thresholds were similarly affected by SAM rate with the lowest thresholds and the largest MR being observed for SAM rates of 1 and 2 Hz at higher masker levels. MR was higher for 32-kHz maskers than for 4-kHz maskers. Increasing signal duration from 500 ms to 2000 ms had minimal effect on MR. The results are discussed with respect to MR resulting from envelope variation and the impact of noise in the environment on target signal detection.
2023 · Laryngo-Rhino-Otologie
This publication investigates Investigation of force relaying elastic elements in the Drosophila melanogaster bona fide mechano-electrical channel NOMPC.
2023 · Biophysical Journal
This publication investigates Cholesterol as a tool to probe the role of membrane in cochlear hair cell mechanotransduction.
2023 · Frontiers in Neuroscience
Introduction Understanding speech in a noisy environment, as opposed to speech in quiet, becomes increasingly more difficult with increasing age. Using the quiet-aged gerbil, we studied the effects of aging on speech-in-noise processing. Specifically, behavioral vowel discrimination and the encoding of these vowels by single auditory-nerve fibers were compared, to elucidate some of the underlying mechanisms of age-related speech-in-noise perception deficits. Methods Young-adult and quiet-aged Mongolian gerbils, of either sex, were trained to discriminate a deviant naturally-spoken vowel in a sequence of vowel standards against a speech-like background noise. In addition, we recorded responses from single auditory-nerve fibers of young-adult and quiet-aged gerbils while presenting the same speech stimuli. Results Behavioral vowel discrimination was not significantly affected by aging. For both young-adult and quiet-aged gerbils, the behavioral discrimination between /eː/ and /iː/ was more difficult to make than /eː/ vs. /aː/ or /iː/ vs. /aː/, as evidenced by longer response times and lower d’ values. In young-adults, spike timing-based vowel discrimination agreed with the behavioral vowel discrimination, while in quiet-aged gerbils it did not. Paradoxically, discrimination between vowels based on temporal responses was enhanced in aged gerbils for all vowel comparisons. Representation schemes, based on the spectrum of the inter-spike interval histogram, revealed stronger encoding of both the fundamental and the lower formant frequencies in fibers of quiet-aged gerbils, but no qualitative changes in vowel encoding. Elevated thresholds in combination with a fixed stimulus level, i.e., lower sensation levels of the stimuli for old individuals, can explain the enhanced temporal coding of the vowels in noise. Discussion These results suggest that the altered auditory-nerve discrimination metrics in old gerbils may mask age-related deterioration in the central (auditory) system to the extent that behavioral vowel discrimination matches that of the young adults.
2023 · The Laryngoscope
Objective In passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high stresses in rigid passive prostheses, which can result in dislocation, protrusion, and pre‐tension in the annular ligament resulting in unsatisfactory hearing results. Methods In collaboration with MED‐EL, we developed a new passive middle ear prosthesis that features a balanced, centered ball joint between the headplate and shaft of the prosthesis. We compared the sound transmission properties of this new prosthesis with those of a standard rigid prosthesis. Using Laser‐Doppler‐Vibrometry, we measured the sound‐induced velocity of the stapes footplate relative to a given acoustic stimulus. Results The new prosthesis showed equivalent sound transmission characteristics compared to the rigid prosthesis, whereas retaining the ability to compensate for pressure fluctuations due to its ball joint. This ensures good transmission properties even during displacements of the tympanic membrane. Conclusion This development is a further step toward a physiological reconstruction of the ossicular chain. Level of Evidence NA Laryngoscope , 133:1717–1721, 2023
2022 · Laryngo-Rhino-Otologie
This publication investigates Towards identifying force relaying elastic elements in Drosophila melanogaster NOMPC.
2022 · European Archives of Oto-Rhino-Laryngology
Abstract Purpose Injury or inflammation of the middle ear often results in the persistent tympanic membrane (TM) perforations, leading to conductive hearing loss (HL). However, in some cases the magnitude of HL exceeds that attributable by the TM perforation alone. The aim of the study is to better understand the effects of location and size of TM perforations on the sound transmission properties of the middle ear. Methods The middle ear transfer functions (METF) of six human temporal bones (TB) were compared before and after perforating the TM at different locations (anterior or posterior lower quadrant) and to different degrees (1 mm, ¼ of the TM, ½ of the TM, and full ablation). The sound-induced velocity of the stapes footplate was measured using single-point laser-Doppler-vibrometry (LDV). The METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated. Results The measured and calculated METF showed frequency and perforation size dependent losses at all perforation locations. Starting at low frequencies, the loss expanded to higher frequencies with increased perforation size. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than anterior perforations. The asymmetry of the TM causes the malleus-incus complex to rotate and results in larger deflections in the posterior TM quadrants than in the anterior TM quadrants. Simulations in the FE model with a sealed cavity show that small perforations lead to a decrease in TM rigidity and thus to an increase in oscillation amplitude of the TM mainly above 1 kHz. Conclusion Size and location of TM perforations have a characteristic influence on the METF. The correlation of the experimental LDV measurements with an FE model contributes to a better understanding of the pathologic mechanisms of middle-ear diseases. If small perforations with significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.
2022 · Laryngo-Rhino-Otologie
This publication investigates The development of a passive middle ear prosthesis with concentric microsphere joint in the head plate – first results from temporal bone experiments.
2022 · Frontiers in Cell and Developmental Biology
Macroautophagy, an evolutionary conserved catabolic process in the eukaryotic cell, regulates cellular homeostasis and plays a decisive role in self-engulfing proteins, protein aggregates, dysfunctional or damaged organelles, and invading pathogens. Growing evidence from in vivo and in vitro models shows that autophagy dysfunction plays decisive role in the pathogenesis of various neurodegenerative diseases, including Parkinson’s disease (PD). PD is an incurable and second most common neurodegenerative disease characterised by neurological and motor dysfunction accompanied of non-motor symptoms that can also reduce the life quality of patients. Despite the investment in research, the aetiology of the disease is still unknown and the therapies available are aimed mostly at ameliorating motor symptoms. Hence, therapeutics regulating the autophagy pathway might play an important role controlling the disease progression, reducing neuronal loss and even ameliorating non-motor symptoms. In this review, we highlight potential therapeutic opportunities involved in different targeting options like an initiation of autophagy, Leucine-rich repeat kinase 2 (LRRK2) inhibition, mitophagy, lysosomes, lipid metabolism, immune system, gene expression, biomarkers, and also non-pharmacological interventions. Thus, strategies to identify therapeutics targeting the pathways modulating autophagy might hold a future for therapy development against PD.
2022 · Developmental Dynamics
Abstract Background Plasticity‐related genes ( Prgs /PRGs) or lipid phosphate phosphatase‐related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain‐specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation. Results We analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio‐temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non‐neuronal cell lines, and does not localize to the plasma membrane of filopodia. Conclusion We showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling.
2022 · Hearing Research
This publication investigates Speech sound discrimination by Mongolian gerbils.
2022 · Protein & Peptide Letters
Abstract: Protein tyrosine phosphatase receptor-type Q (PTPRQ), a member of the type III tyrosine phosphatase receptor (R3 PTPR) family, is composed of three domains, including 18 extracellular fibronectin type III (FN3) repeats, a transmembrane helix, and a cytoplasmic phosphotyrosine phosphatase (PTP) domain. PTPRQ was initially identified as a transcript upregulated in glomerular mesangial cells in a rat model of glomerulonephritis. Subsequently, studies found that PTPRQ has phosphotyrosine phosphatase and phosphatidylinositol phosphatase activities and can regulate cell proliferation, apoptosis, differentiation, and survival. Further in vivo studies showed that PTPRQ is necessary for the maturation of cochlear hair bundles and is considered a potential gene for deafness. In the recent two decades, 21 mutations in PTPRQ have been linked to autosomal recessive hearing loss (DFNB84) and autosomal dominant hearing loss (DFNA73). Recent mutations, deletions, and amplifications of PTPRQ have been observed in many types of cancers, which indicate that PTPRQ might play an essential role in the development of many cancers. In this review, we briefly describe PTPRQ structure and enzyme activity and focus on the correlation between PTPRQ and human disease. A profound understanding of PTPRQ could be helpful in the identification of new therapeutic targets to treat associated diseases.
2022 · European Journal of Neuroscience
Abstract Schroeder‐phase harmonic tone complexes have been used in physiological and psychophysical studies in several species to gain insight into cochlear function. Each pitch period of the Schroeder stimulus contains a linear frequency sweep; the duty cycle, sweep velocity, and direction are controlled by parameters of the phase spectrum. Here, responses to a range of Schroeder‐phase harmonic tone complexes were studied both behaviorally and in neural recordings from the auditory nerve and inferior colliculus of Mongolian gerbils. Gerbils were able to discriminate Schroeder‐phase harmonic tone complexes based on sweep direction, duty cycle, and/or velocity for fundamental frequencies up to 200 Hz. Temporal representation in neural responses based on the van Rossum spike‐distance metric, with time constants of either 1 ms or related to the stimulus' period, was compared with average discharge rates. Neural responses and behavioral performance were both expressed in terms of sensitivity, d' , to allow direct comparisons. Our results suggest that in the auditory nerve, stimulus fine structure is represented by spike timing, whereas envelope is represented by rate. In the inferior colliculus, both temporal fine structure and envelope appear to be represented best by rate. However, correlations between neural d' values and behavioral sensitivity for sweep direction were strongest for both temporal metrics, for both auditory nerve and inferior colliculus. Furthermore, the high sensitivity observed in the inferior colliculus neural rate‐based discrimination suggests that these neurons integrate across multiple inputs arising from the auditory periphery.
2022 · Neurobiology of Disease
This publication investigates Endophilin-B regulates autophagy during synapse development and neurodegeneration.
2022 · Laryngo-Rhino-Otologie
This publication investigates Die Entwicklung einer passiven Mittelohrprothese mit konzentrischem Mikrokugelgelenk in der Kopfplatte – erste Ergebnisse im Felsenbeinexperiment.
2022 · Journal of Experimental Biology
ABSTRACT The mechanisms of sound localization are actively debated, especially which cues are predominately used and why. Our study provides behavioural data in chickens (Gallus gallus) and relates these to estimates of the perceived physical cues. Sound localization acuity was quantified as the minimum audible angle (MAA) in azimuth. Pure-tone MAA was 12.3, 9.3, 8.9 and 14.5 deg for frequencies of 500, 1000, 2000 and 4000 Hz, respectively. Broadband-noise MAA was 12.2 deg, which indicates excellent behavioural acuity. We determined ‘external cues’ from head-related transfer functions of chickens. These were used to derive ‘internal cues’, taking into account published data on the effect of the coupled middle ears. Our estimates of the internal cues indicate that chickens likely relied on interaural time difference cues alone at low frequencies of 500 and 1000 Hz, whereas at 2000 and 4000 Hz, interaural level differences may be the dominant cue.
2022 · Autophagy in Health and Disease
This publication investigates Altered autophagy on the path to Parkinson’s disease.
2021 · Laryngo-Rhino-Otologie
This publication investigates Untersuchung der Kraftweiterleitung beim Hören Drosophila melanogasters.
2021 · Laryngo-Rhino-Otologie
This publication investigates Probing Force Relay in Drosophila melanogaster Hearing.
2021 · Journal of Agricultural and Food Chemistry
This publication investigates Moringa oleifera: A Tree of Life as a Promising Medicinal Plant for Neurodegenerative Diseases.
2021 · Frontiers in Cell and Developmental Biology
Automatic quantification of image parameters is a powerful and necessary tool to explore and analyze crucial cell biological processes. This article describes two ImageJ/Fiji automated macros to approach the analysis of synaptic autophagy and exosome release from 2D confocal images. Emerging studies point out that exosome biogenesis and autophagy share molecular and organelle components. Indeed, the crosstalk between these two processes may be relevant for brain physiology, neuronal development, and the onset/progression of neurodegenerative disorders. In this context, we describe here the macros “Autophagoquant” and “Exoquant” to assess the quantification of autophagosomes and exosomes at the neuronal presynapse of the Neuromuscular Junction (NMJ) in Drosophila melanogaster using confocal microscopy images. The Drosophila NMJ is a valuable model for the study of synapse biology, autophagy, and exosome release. By use of Autophagoquant and Exoquant, researchers can have an unbiased, standardized, and rapid tool to analyze autophagy and exosomal release in Drosophila NMJ. Code available at: https://github.com/IreneSaMi/Exoquant-Autophagoquant
2021 · European Archives of Oto-Rhino-Laryngology
Abstract Purpose Cone Beam Computed Tomography (CBCT) offers a valid alternative to conventional Computed Tomography (CT). A possible radiation dose reduction with the use of CBCT in postoperative imaging of CIs is of great importance. Whether the visualization of Cochlear Implant (CI) electrodes in CBCT correlates with the radiation dose applied was investigated in this study. Methods We compared the visualization quality of Contour Advance CIs to Straight CIs from Cochlear using CBCT with varying tube parameters on whole-head specimen. Results The internal diameter of the cochlea decreases from base to apex, resulting in a significantly different intracochlear positioning of the two tested CI models. While electrodes of the Contour Advance series are located close to the modiolus, thus closer to the spiral ganglion neurons, those of the Straight series are located further away. The artifact portion of the electrode amounts to 50–70% of the radiological diameter of the electrode. An increase in artifact portion from the base (electrode #1 approx. 50%) to the apex (electrode #20 approx. 70%) of the cochlea was observed. The visualization of electrodes in the medial and apical part of the cochlea is limited due to artifact overlapping. There was no correlation between the artifact size and the applied radiation dose. Conclusion The results indicate that a reduction of the radiation dose by up to 45% of the currently applied radiation dose of standard protocols would be possible. Investigations of the effects on subjective image quality still need to be performed.
2021 · Neurobiology of Aging
This publication investigates Age-related decline in cochlear ribbon synapses and its relation to different metrics of auditory-nerve activity.
2020 · The Journal of Neuroscience
People suffering from age-related hearing loss typically present with deficits in temporal processing tasks. Temporal processing deficits have also been shown in single-unit studies at the level of the auditory brainstem, midbrain, and cortex of aged animals. In this study, we explored whether temporal coding is already affected at the level of the input to the central auditory system. Single-unit auditory nerve fiber recordings were obtained from 41 Mongolian gerbils of either sex, divided between young, middle-aged, and old gerbils. Temporal coding quality was evaluated as vector strength in response to tones at best frequency, and by constructing shuffled and cross-stimulus autocorrelograms, and reverse correlations, from responses to 1 s noise bursts at 10–30 dB sensation level (dB above threshold). At comparable sensation levels, all measures showed that temporal coding was not altered in auditory nerve fibers of aging gerbils. Furthermore, both temporal fine structure and envelope coding remained unaffected. However, spontaneous rates were decreased in aging gerbils. Importantly, despite elevated pure tone thresholds, the frequency tuning of auditory nerve fibers was not affected. These results suggest that age-related temporal coding deficits arise more centrally, possibly due to a loss of auditory nerve fibers (or their peripheral synapses) but not due to qualitative changes in the responses of remaining auditory nerve fibers. The reduced spontaneous rate and elevated thresholds, but normal frequency tuning, of aged auditory nerve fibers can be explained by the well known reduction of endocochlear potential due to strial dysfunction in aged gerbils. SIGNIFICANCE STATEMENT As our society ages, age-related hearing deficits become ever more prevalent. Apart from decreased hearing sensitivity, elderly people often suffer from a reduced ability to communicate in daily settings, which is thought to be caused by known age-related deficits in auditory temporal processing. The current study demonstrated, using several different stimuli and analysis techniques, that these putative temporal processing deficits are not apparent in responses of single-unit auditory nerve fibers of quiet-aged gerbils. This suggests that age-related temporal processing deficits may develop more central to the auditory nerve, possibly due to a reduced population of active auditory nerve fibers, which will be of importance for the development of treatments for age-related hearing disorders.
2020 · Proceedings of the National Academy of Sciences
Significance The tiny insect renal (Malpighian) tubule can transport fluid at unparalleled speed, suggesting unique specializations. Here we show that strategic allocation of major intrinsic proteins (MIPs) to specific cells within the tubule allows the separation of metabolically intense active cation transport from passive chloride and water conductance. This specialized renal architecture is general to at least many higher insects, providing a clue to the unique success of the class Insecta in colonizing an extraordinary range of ecological niches.
2020 · European Journal of Neuroscience
Abstract In the analysis of acoustic scenes, we easily miss sounds or are insensitive to sound features that are salient if presented in isolation. This insensitivity that is not due to interference in the inner ear is termed informational masking (IM). So far, the cellular mechanisms underlying IM remained elusive. Here, we apply a sequential IM paradigm to humans and gerbils using a sound level increment detection task determining the sensitivity to target tones in a background of standard (same frequency) and distracting tones (varying in level and frequency). The amount of IM that was indicated by the level increment thresholds depended on the frequency separation between the distracting and the standard and target tones. In humans and gerbils, we observed similar perceptual thresholds. A release from IM of more than 20 dB was observed in both species if the distracting tones were well segregated in frequency from the other tones. Neuronal rate responses elicited by similar sequences in gerbil inferior colliculus and auditory cortex were recorded. At both levels of the auditory pathway, the neuronal thresholds obtained with a signal‐detection‐theoretic approach deducing the sensitivity from the analysis of the neurons’ receiver operating characteristics matched the psychophysical thresholds revealing that IM already emerges at midbrain level. By applying objective response measures in physiology and psychophysics, we demonstrated that the population of neurons has a sufficient sensitivity for explaining the perceptual level increment thresholds indicating IM. There was a good correspondence between the neuronal and perceptual release from IM being related to auditory stream segregation.
2020 · Faculty Reviews
This publication investigates Recent advances in cochlear hair cell nanophysiology: subcellular compartmentalization of electrical signaling in compact sensory cells.
2020 · Laryngo-Rhino-Otologie
This publication investigates Probing Force Relay in Drosophila Hearing.
2020 · Laryngo-Rhino-Otologie
This publication investigates Nitinol in passive ossicular reconstruction - first preclinical results.
2020 · Laryngo-Rhino-Otologie
This publication investigates Nitinol in der passiven Mittelohrchirurgie - erste präklinische Ergebnisse.
2020 · Otology & Neurotology
Hypothesis: Nitinol is a suitable material for passive middle ear prosthesis. Background: In modern ear microsurgery, the restitution of hearing is tremendously important. In passive ossicular reconstruction, rigid alloplastic materials are widespread in use. However, rigid prostheses fail to adapt to atmospheric pressure changes. We describe the use of the super-elastic material nitinol in passive ossicular reconstruction to overcome this limitation. Methods: Together with an industrial partner, we developed a nitinol clip prosthesis equipped with a flexible prosthesis headplate. The new prosthesis was evaluated for flexibility and its sound transmission properties were compared with standard clip prostheses. For this purpose, the sound-induced acceleration of the stapes footplate was measured by laser-doppler vibrometry in temporal bones. Furthermore, the flexibility of the prosthesis plate was tested in a load-cell experiment. Results: On average, the pure tone transmission characteristics of the nitinol prosthesis is statistically not distinguishable from standard titanium clip prostheses. The tests in the load cell confirmed the flexibility of the prosthesis. Any measured prosthesis returns to its original state after deformation. Conclusion: The newly developed nitinol clip prosthesis shows similar sound transmission properties in comparison to established prostheses with high flexibility indicating a step forward to a physiological ossicular chain reconstruction.
2020 · Molecular Imaging and Biology
This publication investigates GABA<inf>A</inf> Receptors in the Mongolian Gerbil: a PET Study Using [<sup>18</sup>F]Flumazenil to Determine Receptor Binding in Young and Old Animals.
2020 · mBio
Secondary metabolites play important roles in microbial communities, but their natural functions are often unknown and may be more complex than appreciated. While compounds with antibiotic activity are often assumed to underlie microbial competition, they may alternatively act as signal molecules. In either scenario, microorganisms might evolve responses to sublethal concentrations of these metabolites, either to protect themselves from inhibition or to change certain behaviors in response to the local abundance of another species. Here, we report that violacein production by C. violaceum ATCC 31532 is induced in response to hygromycin A from Streptomyces sp. 2AW, and we show that this response is dependent on inhibition of translational polypeptide elongation and a previously uncharacterized two-component regulatory system. The breadth of the transcriptional response beyond violacein induction suggests a surprisingly complex metabolite-mediated microbe-microbe interaction and supports the hypothesis that antibiotics evolved as signal molecules. These novel insights will inform predictive models of soil community dynamics and the unintended effects of clinical antibiotic administration.
2019 · bioRxiv
Abstract Insects are highly successful, in part through an excellent ability to osmoregulate. The renal (Malpighian) tubules can secrete fluid faster on a per-cell basis than any other epithelium, but the route for these remarkable water fluxes has not been established. In Drosophila melanogaster , we show that 4 members of the Major Intrinsic Protein family are expressed at very high level in the fly renal tissue; the aquaporins Drip and Prip, and the aquaglyceroporins Eglp2 and Eglp4. As predicted from their structure and by their transport function by expressing these proteins in Xenopus oocytes, Drip, Prip and Eglp2 show significant and specific water permeability, whereas Eglp2 and Eglp4 show very high permeability to glycerol and urea. Knockdowns of any of these genes impacts tubule performance resulting in impaired hormone-induced fluid secretion. The Drosophila tubule has two main secretory cell types: active cation-transporting principal cells with the aquaglyceroporins localize to opposite plasma membranes and small stellate cells, the site of the chloride shunt conductance, with these aquaporins localising to opposite plasma membranes. This suggests a model in which cations are pumped by the principal cells, causing chloride to follow through the stellate cells in order to balance the charge. As a consequence, osmotically obliged water follows through the stellate cells. Consistent with this model, fluorescently labelled dextran, an in vivo marker of membrane water permeability, is trapped in the basal infoldings of the stellate cells after kinin diuretic peptide stimulation, confirming that these cells provide the major route for transepithelial water flux. The spatial segregation of these components of epithelial water transport may help to explain the unique success of the higher insects. Significance statement The tiny insect renal (Malpighian) tubule can transport fluid at unparalleled speed, suggesting unique specialisations. Here we show that strategic allocation of Major Intrinsic Proteins (MIPs) to specific cells within the polarized tubule allow the separation of metabolically intense active cation transport from chloride and water conductance. This body plan is general to at least many higher insects, providing a clue to the unique success of the class Insecta.
2019 · Laryngo-Rhino-Otologie
This publication investigates The influence of tympanic membrane defects on the transfer function of the middle ear.
2019 · American Journal of Physiology-Renal Physiology
Nephrolithiasis is one of the most common kidney diseases, with poorly understood pathophysiology, but experimental study has been hindered by lack of experimentally tractable models. Drosophila melanogaster is a useful model organism for renal diseases because of genetic and functional similarities of Malpighian (renal) tubules with the human kidney. Here, we demonstrated function of the sex-determining region Y protein-interacting protein-1 ( Sip1) gene, an ortholog of human Na + /H + exchanger regulatory factor ( NHERF1), in Drosophila Malpighian tubules and its impact on nephrolithiasis. Abundant birefringent calculi were observed in Sip1 mutant flies, and the phenotype was also observed in renal stellate cell-specific RNA interference Sip1 knockdown in otherwise normal flies, confirming a renal etiology. This phenotype was abolished in rosy mutant flies (which model human xanthinuria) and by the xanthine oxidase inhibitor allopurinol, suggesting that the calculi were of uric acid. This was confirmed by direct biochemical assay for urate. Stones rapidly dissolved when the tubule was bathed in alkaline media, suggesting that Sip1 knockdown was acidifying the tubule. SIP1 was shown to collocate with Na + /H + exchanger isoform 2 (NHE2) and with moesin in stellate cells. Knockdown of NHE2 specifically to the stellate cells also increased renal uric acid stone formation, and so a model was developed in which SIP1 normally regulates NHE2 activity and luminal pH, ultimately leading to uric acid stone formation. Drosophila renal tubules may thus offer a useful model for urate nephrolithiasis.
2019 · NeuroImage: Clinical
This publication investigates Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder.
2019 · Methods in Molecular Biology
This publication investigates Epithelial function in the Drosophila Malpighian Tubule: An in vivo renal model.
2019 · Laryngo-Rhino-Otologie
This publication investigates Der Einfluss von Trommelfelldefekten auf die Transferfunktion des Mittelohres.
2019 · Current Biology
This publication investigates Chromophore-Independent Roles of Opsin Apoproteins in Drosophila Mechanoreceptors.
2019 · Laryngo-Rhino-Otologie
This publication investigates Cell membrane lipids affect the mechano-electrical transduction channel. PIP2 (phosphatidylinositol-4,5-bisphosphat) specifically modulating single channel conductance and ion selectivity.
2018 · Science Advances
Inspired from plant medicine, a drug that partially compensates for memory decline in aged flies and mice is identified.
2018 · Journal of Comparative Physiology A
This publication investigates Interaction of interaural cues and their contribution to the lateralisation of Mongolian gerbils (Meriones unguiculatus).
2018 · Rejuvenation Research
Aging is a complex process resulting in (1) a decline in body functions and capacity to withstand environmental stress and (2) an increased susceptibility to diseases including, but not limited to, cardiovascular disorders, diabetes, cancer, and dementia. Among a number of herbal products used to alleviate symptoms associated with aging is Ilex paraguariensis (IP). This product has been reported to have anticancer, anti-inflammatory, and antioxidant activities. However, its effect on an organisms' longevity has not been thoroughly studied to date. Here, we report that 10 mg/mL IP supplementation significantly extended the lifespan of Drosophila . Additionally, IP enhanced flies' ability to resist environmental stress as estimated using starvation, paraquat, and desiccation assays. Additional experiments revealed insignificant changes in weight gain, physical activity, and metabolic profiles such as levels of water, lipid, and protein in flies receiving IP supplementation. Rather, levels of messenger RNA for enzymes that scavenge reactive oxygen species ( i.e. , superoxide dismutases, catalase, and glutathione peroxidase) were found to be significantly altered despite subtle changes in their catalytic activities. We hope that our research demonstrating IP-induced lifespan extension and related biological mechanisms of this interesting phenomenon will encourage further studies, which may eventually determine whether IP has utility as a novel antiaging agent.
2018 · European Journal of Nuclear Medicine and Molecular Imaging
This publication investigates F-18-Flumazenil PET of GABA(A) receptor binding in the Mongolian gerbil - comparison of different approaches for quantification and age dependency of results.
2018 · AIP Conference Proceedings
This publication investigates Cell membrane organization is important for inner hair cell MET-channel gating.
2018 · Brain Structure and Function
This publication investigates Activation in the auditory pathway of the gerbil studied with <sup>18</sup> F-FDG PET: effects of anesthesia.
2017 · The Journal of Neuroscience
Membrane proteins, such as ion channels, interact dynamically with their lipid environment. Phosphoinositol-4,5-bisphosphate (PIP 2 ) can directly or indirectly modify ion-channel properties. In auditory sensory hair cells of rats (Sprague Dawley) of either sex, PIP 2 localizes within stereocilia, near stereocilia tips. Modulating the amount of free PIP 2 in inner hair-cell stereocilia resulted in the following: (1) the loss of a fast component of mechanoelectric-transduction current adaptation, (2) an increase in the number of channels open at the hair bundle's resting position, (3) a reduction of single-channel conductance, (4) a change in ion selectivity, and (5) a reduction in calcium pore blocking effects. These changes occur without altering hair-bundle compliance or the number of functional stereocilia within a given hair bundle. Although the specific molecular mechanism for PIP 2 action remains to be uncovered, data support a hypothesis for PIP 2 directly regulating channel conformation to alter calcium permeation and single-channel conductance. SIGNIFICANCE STATEMENT How forces are relayed to the auditory mechanoelectrical transduction (MET) channel remains unknown. However, researchers have surmised that lipids might be involved. Previous work on bullfrog hair cells showed an effect of phosphoinositol-4,5-bisphosphate (PIP 2 ) depletion on MET current amplitude and adaptation, leading to the postulation of the existence of an underlying myosin-based adaptation mechanism. We find similar results in rat cochlea hair cells but extend these data to include single-channel analysis, hair-bundle mechanics, and channel-permeation properties. These additional data attribute PIP 2 effects to actions on MET-channel properties and not motor interactions. Further findings support PIP 2 's role in modulating a fast, myosin-independent, and Ca 2+ -independent adaptation process, validating fast adaptation's biological origin. Together this shows PIP 2 's pivotal role in auditory MET, likely as a direct channel modulator.
2017 · eLife
Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.
2017 · Biogerontology
This publication investigates Jujube (Ziziphus Jujuba Mill.) fruit feeding extends lifespan and increases tolerance to environmental stresses by regulating aging-associated gene expression in Drosophila.
2017 · PLOS ONE
This publication investigates Exploring binaural hearing in gerbils (Meriones unguiculatus) using virtual headphones.
2017 · European Journal of Neuroscience
Abstract Prior stimulation can influence the perception of sound source location. Some psychophysical sound localization procedures differ in the amount of prior stimulation, which may affect measures of localization accuracy. If and how particularly the number of preceding stimuli affects sound localization and the neural representation of sound source position has not been investigated so far and will be the focus of the present report. We trained Mongolian gerbils in a left/right discrimination task where the target stimulus was preceded by silence or followed a number of reference stimuli. Localization thresholds decreased with the number of references presented before the target stimulus. The smallest thresholds were found after the presentation of a train of 5 reference stimuli and after silence. We recorded from units in the inferior colliculus ( IC ) of anaesthetized gerbils using virtual‐acoustic space stimuli mimicking the ones used in the behavioural task and applied signal detection theory to compare behavioural and neurometric thresholds. We found that neurometric thresholds based on spike rate information of single units covered a wide range of threshold values but only neurometric thresholds that were based on responses of small populations of IC units reached consistently thresholds we also observed in the behavioural experiment. Unlike behavioural thresholds, however, neurometric thresholds were independent of the number of reference stimuli suggesting that processing stages downstream from the IC might better reflect the effect of prior stimulation.
2016 · Advances in Experimental Medicine and Biology
This publication investigates Moving objects in the barn owl’s auditory world.
2016 · Hearing Research
This publication investigates Aging effects on the binaural interaction component of the auditory brainstem response in the Mongolian gerbil: Effects of interaural time and level differences.
2016 · The Journal of the Acoustical Society of America
Auditory models have been developed for decades to simulate characteristics of the human auditory system, but it is often unknown how well auditory models compare to each other or perform in tasks they were not primarily designed for. This study systematically analyzes predictions of seven publicly-available cochlear filter models in response to a fixed set of stimuli to assess their capabilities of reproducing key aspects of human cochlear mechanics. The following features were assessed at frequencies of 0.5, 1, 2, 4, and 8 kHz: cochlear excitation patterns, nonlinear response growth, frequency selectivity, group delays, signal-in-noise processing, and amplitude modulation representation. For each task, the simulations were compared to available physiological data recorded in guinea pigs and gerbils as well as to human psychoacoustics data. The presented results provide application-oriented users with comprehensive information on the advantages, limitations and computation costs of these seven mainstream cochlear filter models.
2015 · Pflügers Archiv - European Journal of Physiology
This publication investigates The how and why of identifying the hair cell mechano-electrical transduction channel.
2015 · Cell Reports
This publication investigates The adhesion GPCR latrophilin/CIRL shapes mechanosensation.
2015 · Oxidative Medicine and Cellular Longevity
Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.
2015 · Frontiers in Human Neuroscience
This publication investigates Electrocorticographic representations of segmental features in continuous speech.
2015 · Journal of Clinical Investigation
This publication investigates Designer aminoglycosides prevent cochlear hair cell loss and hearing loss.
2015 · Biomolecules & Therapeutics
This publication investigates Defensive behavior against noxious heat stimuli is declined with aging due to decreased pain-associated gene expression in Drosophila.
2015 · The Journal of the Acoustical Society of America
Although auditory brainstem responses (ABRs), the sound-evoked brain activity in response to transient sounds, are routinely measured in humans and animals there are often differences in ABR waveform morphology across studies. One possible reason may be the method of stimulus calibration. To explore this hypothesis, click-evoked ABRs were measured from seven ears in four Mongolian gerbils (Meriones unguiculatus) using three common spectrum calibration strategies: Minimum phase filter, linear phase filter, and no filter. The results show significantly higher ABR amplitude and signal-to-noise ratio, and better waveform resolution with the minimum phase filtered click than with the other strategies.
2014 · Frontiers in Neuroscience
This publication investigates Hybrid fNIRS-EEG based classification of auditory and visual perception processes.
2014 · Nature Neuroscience
This publication investigates Corrigendum: Direct gating and mechanical integrity of Drosophila auditory transducers require TRPN1.
