Comparison of three spike detectors dedicated to single unit action potentials of the auditory nerve

International audienceThis paper compares three methods for the detection of single unit action potentials in auditory nerve. The detector structures are similar consisting of a filtering procedure in the first stage and a decision rule in the second stage. The detection accuracy of each detector is characterized by the couple probability of a true detection vs. rates of false detection with synthetic data. The performance comparison between detectors shows that the detector using a band-pass finite-impulse-response filter with complex coefficients offers the best performance. This observation was especially evident for low signal to noise ratios. This finding is confirmed with real data and leads us to revise the protocol of spike detection in auditory nerve

Age-related Changes in Auditory Cortex Without Detectable Peripheral Alterations: A Multi-level Study in Sprague–Dawley Rats

International audienceAging is often considered to affect both the peripheral (i.e. the cochlea) and central (brainstem and thalamus-cortex) auditory systems. We investigated the effects of aging on the cochlea, brainstem and cortex of female Sprague-Dawley rats. The auditory nerve threshold remained stable between the ages of nine and 21 months, as did distortion product otoa-coustic emissions and the number of ribbon synapses between inner hair cells and nerve fibers. The first clear signs of aging appeared in the brainstem, in which response amplitude decreased, with thresholds remaining stable until the age of 15 months, and increasing slightly thereafter. The responses of primary auditory cortex neurons revealed specific effects of aging: at 21 months, receptive fields were spectrally narrower and the temporal reliability of responses to communication sounds was lower. However, aging had a null or even positive effect on neuronal responses in the presence of background noise, responses to amplitude-modulated sounds, and responses in gap-detection protocols. Overall, inter-animal variability remained high relative to the variability across groups of different ages, for all parameters tested. Beha-vioral performance for the modulation depth of amplitude modulation noise was worse in 21-month old animals than in other animals. Age-related alterations of cortical and behavioral responses were thus observed in animals displaying no signs of aging at the peripheral level. These results suggest that intrinsic, central aging effects can affect the perception of acoustic stimuli independently of the effects of aging on peripheral receptors

Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression

Before acquiring their mature state, cochlear hair cells undergo a series of changes in expression of ion channels. How this complex mechanism is achieved is not fully understood. Tmprss3, a type II serine protease expressed in hair cells, is required for their proper functioning at the onset of hearing. To unravel the role of Tmprss3 in the acquisition of mature K+ currents, we compared their function by patch-clamp technique in wild-type Tmprss3WT and Tmprss3Y260X-mutant mice. Interestingly, only outward K+ currents were altered in Tmprss3Y260X-mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3WT and Tmprss3Y260X-mutant mice using proteomic analysis. This led to the identification of a pathway related to potassium Kcnma1 channels. This pathway was validated by immunohistochemistry, focusing on the most downregulated protein that was identified as a cochlear Kcnma1-associated protein, APOA1. Finally, we show that, in contrast to Tmprss3WT, Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3Y260X-mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs

Spiking Pattern of the Mouse Developing Inner Hair Cells Is Mostly Invariant Along the Tonotopic Axis

During development, the sensory cells of the cochlea, the inner hair cells (IHCs), fire spontaneous calcium action potentials. This activity at the pre-hearing stage allows the IHCs to autonomously excite the auditory nerve fibers and hence, represents an efficient mechanism to shape the tonotopic organization along the ascending auditory pathway. Using calcium imaging, we show that the activity in the developing cochlea consists of calcium waves that propagate across the supporting and sensory cells. Both basal and apical IHCs were characterized by similar spontaneous calcium transients interspaced with silent periods, consistent with bursts of action potentials recorded in patch-clamp. In addition, adjacent auditory hair cells tend to have a synchronized [Ca2+]i activity, irrespective of their location along the base-to-apex gradient of the cochlea. Finally, we show that the mechanical ablation of the inner phalangeal cells (IPCs), a class of supporting cells, reduces the synchronized [Ca2+]i activity between neighboring sensory cells. These findings support the hypothesis that the tonotopic map refinement in higher auditory centers would depend on the synchronization of a discrete number of auditory sensory cells

Comparative actions of salicylate on the amphibian lateral line and guinea pig cochlea

1. 1. Salicylate actions on afferent nerve activity in the Xenopus lateral line and on cochlear potentials in guinea pig were investigated.2. 2. In the lateral line, salicylate (0.3-2.5 mM) suppressed spontaneous activity, water motion evoked excitation and responses to -glutamate (1-2 mM) and kainate (10-20[mu]M).3. 3. In the guinea pig, salicylate (0.6-10 mM) suppressed the compound action potential (CAP) and increased N1 latency at low but not high sound intensities.4. 4. In the lateral line salicylate action may involve an antagonism of the hair-cell transmitter on the afferent nerve.5. 5. In the cochlea salicylate may suppress the active process or cochlear amplifier.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28123/1/0000573.pd

Echolocating whales and bats express the motor protein prestin in the inner ear: a potential marker for hearing loss

Prestin is an integral membrane motor protein located in outer hair cells of the mammalian cochlea. It is responsible for electromotility and required for cochlear amplification. Although prestin works in a cycle-by-cycle mode up to frequencies of at least 79 kHz, it is not known whether or not prestin is required for the extreme high frequencies used by echolocating species. Cetaceans are known to possess a prestin coding gene. However, the expression and distribution pattern of the protein in the cetacean cochlea has not been determined, and the contribution of prestin to echolocation has not yet been resolved. Here we report the expression of the protein prestin in five species of echolocating whales and two species of echolocating bats. Positive labelling in the basolateral membrane of outer hair cells, using three anti-prestin antibodies, was found all along the cochlear spiral in echolocating species. These findings provide morphological evidence that prestin can have a role in cochlear amplification in the basolateral membrane up to 120-180 kHz. In addition, labelling of the cochlea with a combination of anti-prestin, anti-neurofilament, anti-myosin VI and/or phalloidin and DAPI will be useful for detecting potential recent cases of noise-induced hearing loss in stranded cetaceans. This study improves our understanding of the mechanisms involved in sound transduction in echolocating mammals, as well as describing an optimized methodology for detecting cases of hearing loss in stranded marine mammals

Weakly Consistent Regularisation Methods for Ill-Posed Problems

This Chapter takes its origin in the lecture notes for a 9 h course at the Institut Henri Poincaré in September 2016. The course was divided in three parts. In the first part, which is not included herein, the aim was to first recall some basic aspects of stabilised finite element methods for convection-diffusion problems. We focus entirely on the second and third parts which were dedicated to ill-posed problems and their approximation using stabilised finite element methods. First we introduce the concept of conditional stability. Then we consider the elliptic Cauchy-problem and a data assimilation problem in a unified setting and show how stabilised finite element methods may be used to derive error estimates that are consistent with the stability properties of the problem and the approximation properties of the finite element space. Finally, we extend the result to a data assimilation problem subject to the heat equation

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population