Distinct integration of spectrally complex sounds in mouse primary auditory cortices.

The standard hierarchical signal transmission along the lemniscal auditory pathway in mice changes in the cortex, where two tonotopically organized auditory regions receive thalamic inputs in parallel: the primary auditory cortex (A1) and the anterior auditory field (AAF). These fields show distinct properties of sound-evoked responses, where A1 responds robustly to sound onset and AAF exhibits faster and more transient responses following both sound onset and offset. Previous reports showed a strong involvement of AAF in temporal processing, revealing its particular role in encoding temporal information. A more regular tonotopy, narrower frequency response areas, and more robust direction selectivity to frequency modulated sweeps led to the speculation that A1 codes better the spectral composition of a sound than AAF. However, potential mechanisms explaining why A1 favors spectral processing have not been previously described. Using in vivo electrophysiological recordings in the mouse auditory cortex, we found that A1 neurons, unlike AAF neurons, respond stronger and faster to spectrally complex tones than to pure tones. Next, we show that both regular and putative fast-spiking neurons in A1, but not in AAF, display larger responses to spectrally complex tones than to pure tones. Finally, we use a laminar analysis to demonstrate that A1 neurons in layer 2/3 respond stronger to spectrally complex tones than neurons in layer 4, indicating an important transformation of the neural representation of spectral complexity between thalamo-recipient and supragranular layers in A1, but not in AAF. Our study reveals circuit features contributing to distinct processing of spectrally simple and complex sounds in the two primary auditory cortices and supports a dual-stream processing in the core auditory cortex.

Emergence and function of cortical offset responses in sound termination detection.

Offset responses in auditory processing appear after a sound terminates. They arise in neuronal circuits within the peripheral auditory system, but their role in the central auditory system remains unknown. Here, we ask what the behavioral relevance of cortical offset responses is and what circuit mechanisms drive them. At the perceptual level, our results reveal that experimentally minimizing auditory cortical offset responses decreases the mouse performance to detect sound termination, assigning a behavioral role to offset responses. By combining in vivo electrophysiology in the auditory cortex and thalamus of awake mice, we also demonstrate that cortical offset responses are not only inherited from the periphery but also amplified and generated de novo. Finally, we show that offset responses code more than silence, including relevant changes in sound trajectories. Together, our results reveal the importance of cortical offset responses in encoding sound termination and detecting changes within temporally discontinuous sounds crucial for speech and vocalization.

A Late Critical Period for Frequency Modulated Sweeps in the Mouse Auditory System.

Neuronal circuits are shaped by experience during time windows of increased plasticity in postnatal development. In the auditory system, the critical period for the simplest sounds-pure frequency tones-is well defined. Critical periods for more complex sounds remain to be elucidated. We used in vivo electrophysiological recordings in the mouse auditory cortex to demonstrate that passive exposure to frequency modulated sweeps (FMS) from postnatal day 31 to 38 leads to long-term changes in the temporal representation of sweep directions. Immunohistochemical analysis revealed a decreased percentage of layer 4 parvalbumin-positive (PV+) cells during this critical period, paralleled with a transient increase in responses to FMS, but not to pure tones. Preventing the PV+ cell decrease with continuous white noise exposure delayed the critical period onset, suggesting a reduction in inhibition as a mechanism for this plasticity. Our findings shed new light on the dependence of plastic windows on stimulus complexity that persistently sculpt the functional organization of the auditory cortex.

Distinct processing of tone offset in two primary auditory cortices.

In the rodent auditory system, the primary cortex is subdivided into two regions, both receiving direct inputs from the auditory thalamus: the primary auditory cortex (A1) and the anterior auditory field (AAF). Although neurons in the two regions display different response properties, like response latency, firing threshold or tuning bandwidth, it is still not clear whether they process sound in a distinct way. Using in vivo electrophysiological recordings in the mouse auditory cortex, we found that AAF neurons have significantly stronger responses to tone offset than A1 neurons. AAF neurons also display faster and more transient responses than A1 neurons. Additionally, offset responses in AAF - unlike in A1, increase with sound duration. Local field potential (LFP) and laminar analyses suggest that the differences in sound responses between these two primary cortices are both of subcortical and intracortical origin. These results emphasize the potentially critical role of AAF for temporal processing. Our study reveals a distinct role of two primary auditory cortices in tone processing and highlights the complexity of sound encoding at the cortical level.

Streptococcus pneumoniae-induced ototoxicity in organ of Corti explant cultures.

Hearing loss remains the most common long-term complication of pneumococcal meningitis (PM) reported in up to 30% of survivors. Streptococcus pneumoniae have been shown to possess different ototoxic properties. Here we present a novel ex vivo experimental setup to examine in detail the pattern of hair cell loss upon exposure to different S. pneumoniae strains, therefore recapitulating pathogen derived aspects of PM-induced hearing loss. Our results show a higher susceptibility towards S. pneumoniae-induced cochlear damage for outer hair cells (OHC) compared to inner hair cells (IHC), which is consistent with in vivo data. S. pneumoniae-induced hair cell loss was both time and dose-dependent. Moreover, we have found significant differences in the level of cell damage between tissue from the basal and the apical turns. This shows that the higher vulnerability of hair cells located at high frequency regions observed in vivo cannot be explained solely by the spatial organisation and bacterial infiltration from the basal portion of the cochlea. Using a wild type D39 strain and a mutant defective for the pneumolysin (PLY) gene, we also have shown that the toxin PLY is an important factor involved in ototoxic damages. The obtained results indicate that PLY can cause both IHC and OHC loss. Finally, we are reporting here for the first time a higher vulnerability of HC located at the basal and middle cochlear region to pneumolysin-induced damage. The detailed description of the susceptibility of hair cells to Streptococcus pneumoniae provided in this report can in the future determine the choice and the development of novel otoprotective therapies during pneumococcal meningitis.

New chamber stapes prosthesis - A preliminary assessment of the functioning of the prototype.

Piston-stapedotomy is the most common method for hearing restoration in patients with otosclerosis. In this study, we have experimentally examined a prototype of a new chamber stapes prosthesis. The prototype was implanted in a human cadaver temporal bone. The round window vibrations before and after implantation were measured for the acoustic signal (90 dB SPL, 0.8-8 kHz) in the external auditory canal. In comparison with a 0.4-mm piston prosthesis, the chamber prosthesis induced significantly higher vibration of the round window, especially for frequencies above 1.5 kHz. Based on the results, it can be surmised that stapedotomy with a chamber stapes prosthesis could provide better hearing results in comparison with the piston-stapedotomy.

The Severity of Infection Determines the Localization of Damage and Extent of Sensorineural Hearing Loss in Experimental Pneumococcal Meningitis.

UNLABELLED: Hearing loss is an important sequela of pneumococcal meningitis (PM), occurring in up to 30% of survivors. The role of the severity of infection on hearing function and pathomorphological consequences in the cochlea secondary to PM have not been investigated to date. Using a well-established model of PM, we systematically investigated the functional hearing outcome and the long-term fate of neurosensory cells in the cochlea, i.e., hair cells and spiral ganglion neurons (SGNs), with a focus on their tonotopic distribution. Intracisternal infection of infant rats with increasing inocula of Streptococcus pneumoniae resulted in a dose-dependent increase in CSF levels of interleukin-1ß, interleukin-6, tumor necrosis factor α, interleukin-10, and interferon-γ in acute disease. The severity of long-term hearing loss at 3 weeks after infection, measured by auditory brainstem response recordings, correlated to the initial inoculum dose and to the levels of proinflammatory cytokines determined in the acute phase of PM. Quantitative cochlear histomorphology revealed a significant loss of SGNs and outer hair cells that strongly correlated to the level of infection, with the most severe damage occurring in the basal part of the cochlea. Inner hair cells (IHCs) were not significantly affected throughout the entire cochlea. However, surviving IHCs lost synaptic connectivity to remaining SGNs in all cochlear regions. These findings provide evidence that the inoculum concentration, i.e., severity of infection, is the major determinant of long-term morphological cell pathologies in the cochlea and functional hearing loss. SIGNIFICANCE STATEMENT: Hearing loss is a neurofunctional deficit occurring in up to 30% of patients surviving pneumococcal meningitis (PM). Here, we analyze the correlation between the severity of infection and the inflammatory response in the CSF, the tonotopic distribution of neurosensory pathologies in the cochlea, and the long-term hearing function in a rat model of pneumococcal meningitis. Our study identifies the severity of infection as the key determinant of long-term hearing loss, underlining the importance of the prompt institution of antibiotic therapy in patients suffering from PM. Furthermore, our findings reveal in detail the spatial loss of cochlear neurosensory cells, providing new insights into the pathogenesis of meningitis-associated hearing loss that reveal new starting points for the development of otoprotective therapies.