Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.

ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain

CNS neurons have no sensory function, protected by the skull. For this reason, brain neuromodulation by ultrasound were either done at a high intensity or through auditory nerves. We demonstrate in this study CNS neurons react to ultrasound stimulation at an intensity (5 mW/cm2) far lower than typical therapeutic ultrasound (>30 mW/cm2). Using micropipette ultrasound in calcium imaging, we show ASIC1a channels play a role in the reactions of CNS neurons to ultrasound, pointing to the molecular basis for direct ultrasound neuromodulation at low intensity. Furthermore, we also show evidence of neurogenesis with the same ultrasound stimulation, suggesting potential therapeutic translation.

Computational Modeling of Information Propagation during the Sleep–Waking Cycle

Non-threatening familiar sounds can go unnoticed during sleep despite the fact that they enter our brain by exciting the auditory nerves. Extracellular cortical recordings in the primary auditory cortex of rodents show that an increase in firing rate in response to pure tones during deep phases of sleep is comparable to those evoked during wakefulness. This result challenges the hypothesis that during sleep cortical responses are weakened through thalamic gating. An alternative explanation comes from the observation that the spatiotemporal spread of the evoked activity by transcranial magnetic stimulation in humans is reduced during non-rapid eye movement (NREM) sleep as compared to the wider propagation to other cortical regions during wakefulness. Thus, cortical responses during NREM sleep remain local and the stimulus only reaches nearby neuronal populations. We aim at understanding how this behavior emerges in the brain as it spontaneously shifts between NREM sleep and wakefulness. To do so, we have used a computational neural-mass model to reproduce the dynamics of the sensory auditory cortex and corresponding local field potentials in these two brain states. Following the synaptic homeostasis hypothesis, an increase in a single parameter, namely the excitatory conductance g¯AMPA, allows us to place the model from NREM sleep into wakefulness. In agreement with the experimental results, the endogenous dynamics during NREM sleep produces a comparable, even higher, response to excitatory inputs to the ones during wakefulness. We have extended the model to two bidirectionally connected cortical columns and have quantified the propagation of an excitatory input as a function of their coupling. We have found that the general increase in all conductances of the cortical excitatory synapses that drive the system from NREM sleep to wakefulness does not boost the effective connectivity between cortical columns. Instead, it is the inter-/intra-conductance ratio of cortical excitatory synapses that should raise to facilitate information propagation across the brain.

The Biophysical Function of the Human Inner Ear

The ear transforms soft mechanical vibration of air particles into electrical signals, which reach the appropriate part of the cerebral cortex for processing by means of auditory nerves. The process of the hearing is next: the eardrum vibrates from the sound waves; auditory ossicles amplify the stimulus; in an oval window, the vibration is transmitted to the fluid space of the inner ear; iIt vibrates the basilar membrane; what is pressed against the membrane tectoria; the stereocilliums of the hair cell bend, ion channels open; hair cell depolarizes; stimulus is dissipated in cerebrospinal fluid VIII (vestibulocochlearis); temporal lobe primary auditory cortex (Brodman 41, 42); association pathways: speech comprehension (Wernicke area). For the rising prevalence of psychoses (mental disorders) in the last decades among towns­people, these stimuli – as compared to the abandoned environment – and the adaptation to them may also play a definite role. The man, therefore, enjoying worths and conveniences of the civilization has to size every opportunity to get into the open, to compensate the monotony of the external stimuli, in a word, to grant his organism those stimuli which he claims as a biological creature. This human demand – it seems – is such a great physiological need that our organism cannot be without even in the evening. At least this turns out according to the researches relating sleep and dreaming.

Sudden Sensorineural Hearing Loss with Auditory Neuropathy: Evidence Based on Audiological Test and Inner Ear MRI

Background: Sudden sensorineural hearing loss (SSNHL), defined as a hearing loss of ≥30 dB affecting at least three consecutive frequencies occurring over a 72-hour period, is commonly in audiologic and otolaryngologic practice. However, SSNHL with auditory neuropathy is rarely reported. We described the clinical characteristics of a patient with SSNHL and auditory neuropathy, together with its etiologic mechanism. Case presentation: A 27-year-old woman was referred to our otological clinic with acute diminished hearing on the left ear, associated with persistent tinnitus, aural fullness and vertigo, all for a duration of 20 days. Audiological examination showed presence of otoacoustic emissions and cochlear microphone with absent ABR on the left ear, which was consistent with the criteria of auditory neuropathy. Magnetic resonance images of the brain and inner ear implicated demyelinating lesions in the auditory nerve. Forty months after onset, all the auditory retests were normal and symmetric T2-FLAIR signals of both auditory nerves were found in inner ear magnetic resonance images.Conclusion: We showed that the SSNHL with auditory neuropathy could be caused by demyelination. The case also suggests that some SSNHL caused by demyelination is reversible.

SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves

Background The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. Results Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. Conclusions These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

On intracerebral endings and connections of the seventh and eighth pairs of cranial nerves

The anatomy of the facial and auditory nerves, thanks to a whole series of studies produced according to all sorts of methods, seems at the present time very thoroughly developed; but while the method of degeneration (with peripheral lesions) has already understood many connections of the facial nerve in a person, it has not yet been possible to observe sufficiently extensive degenerations in the medulla oblongata and tubercles of the quadruple due to damage to the peripheral auditory canals. It is in this last relationship that the case I have studied is of interest, although it should be noted that for the anatomy of the facial nerve, he also understood some still unknown relationship.

Auditory pathways

Until the eighties of the present century, anatomists and neuropathologists developed the question of the endings of the auditory nerves in the medulla oblongata, expressing at the same time many different assumptions about the origins of them in various places of this brain, for them a different number of roots and ascribing to them all possible directions.

SCN11A Gene Deletion Causes Sensorineural Hearing Loss by Impairing the Ribbon Synapses and Auditory Nerves

Background: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. Results: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice in the basal turn was also lower than WT, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Nav1.9 KO mice showed higher and progressive ABR threshold at 16 kHz, a significant increase in CAP thresholds, while no changes in cochlear microphonics (CM). Conclusions: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.