Biology subjects

Liberman, C.

Publications and source records attributed to Liberman, C..

3 recordsLinked to original sources

bioRxiv2025

Cochlear histopathology in macaques after noise-induced temporary threshold shifts

Noise exposures causing transient hearing loss were previously considered benign. However, recent work has revealed that temporary noise-induced threshold shifts may be associated with long-lasting cochlear histopathology. One such effect is cochlear synaptopathy, i.e. changes to the afferent synapse between inner hair cells and auditory nerve fibers. Noise-induced synaptopathy has been extensively characterized in several rodent models, and temporal bone studies suggest similar age-related changes in humans. However, it remains unclear how noise-induced temporary threshold shifts affect cochlear structures in humans and nonhuman primates, which show greater resistance to noise exposure than other animals. Additionally, the long-term sequelae of temporary threshold shifts are largely unknown. Here, we characterized the effects of a noise exposure causing temporary hearing loss on cochlear histopathology in macaque monkeys at long post-exposure survival times. Overall, cochlear histopathology was variable across subjects, similar to the variable susceptibility observed in humans. At 2 and 10 months post-exposure, macaques had no significant loss of hair cells, inner hair cell synapses, or cholinergic efferent innervation. However, enlargement of ribbons in both inner and outer hair cells was observed. Together, these findings provide insight into the cochlear effects of single-exposure temporary threshold shifts in nonhuman primates. HIGHLIGHTS- Macaques exposed to 120 dB SPL noise for 4h showed temporary threshold shifts - Cochlear histopathology was evaluated at 2 and 10 months post-exposure - Macaques had no significant loss of hair cells or inner hair cell synapses - Chronic enlargement of inner and outer hair cell ribbons was observed - Transient loss of outer hair cell ribbons was also observed

neuroscience↗

bioRxiv2024

A modiolar-pillar gradient in auditory-nerve dendritic length: a novel post-synaptic contribution to dynamic range?

Auditory-nerve fibers (ANFs) from a given cochlear region can vary in threshold sensitivity by up to 60 dB, corresponding to a 1000-fold difference in stimulus level, although each fiber innervates a single inner hair cell (IHC) via a single synapse. ANFs with high-thresholds also have low spontaneous rates (SRs) and synapse on the side of the IHC closer to the modiolus, whereas the low-threshold, high-SR fibers synapse on the side closer to the pillar cells. Prior biophysical work has identified modiolar-pillar differences in both pre- and post-synaptic properties, but a comprehensive explanation for the wide range of sensitivities remains elusive. Here, in guinea pigs, we used immunostaining for several neuronal markers, including Caspr, a key protein in nodes of Ranvier, to reveal a novel modiolar-pillar gradient in the location of the first ANF heminodes, presumed to be the site of the spike generator, just outside the sensory epithelium. Along the cochlea, from apex to base, the unmyelinated terminal dendrites of modiolar ANFs were 2 - 4 times longer than those of pillar ANFs. This modiolar-pillar gradient in dendritic length, coupled with the 2 - 4 fold smaller caliber of modiolar dendrites seen in prior single-fiber labeling studies, suggests there could be a large difference in the number of length constants between the synapse and the spike initiation zone for low- vs high-SR fibers. The resultant differences in attenuation of post-synaptic potentials propagating along these unmyelinated dendrites could be a key contributor to the observed range of threshold sensitivities among ANFs.

neuroscience↗

bioRxiv2021

Probing adaptation and spontaneous firing in human auditory-nerve fibers with far-field peri-stimulus time responses

Information in sound stimuli is conveyed from sensory hair cells to the cochlear nuclei by the firing of auditory nerve fibers (ANFs). For obvious ethical reasons, single unit recordings from the cochlear nerve have never been performed in human, thus functional hallmarks of ANFs are unknown. By filtering and rectifying the electrical signal recorded at the round window of gerbil cochleae, we reconstructed a peri-stimulus time response (PSTR), with a waveform similar to the peri-stimulus time histograms (PSTHs) recorded from single ANFs. Pair-by-pair analysis of simultaneous PSTR and PSTH recordings in gerbil provided a model to predict the rapid adaptation and spontaneous discharge rates (SR) in a population of ANFs according to their location in the cochlea. We then probed the model in the mouse, in which the SR-based distribution of ANFs differs from the gerbil. We show that the PSTR-based predictions of the rapid adaptation time constant and mean SR across frequency again matched those obtained by recordings from single ANFs. Using PSTR recorded from the human cochlear nerve in 8 normal-hearing patients who underwent cerebellopontine angle surgeries for a functional cranial-nerve disorders (trigeminal neuralgia or hemifacial spasm), we predicted a rapid adaptation of about 3 milliseconds and a mean SR of 23 spikes/s in the 4 kHz frequency range in human ANFs. Together, our results support the use of PSTR as a promising diagnostic tool to map the auditory nerve in humans, thus opening new avenues to better understanding neuropathies, tinnitus, and hyperacusis.

neuroscience↗