RX6 Multifunction Processor

Sound sources along the azimuth generate interaural time differences in arrival (ITDs) at the ears. According to Jeffress’ hypothesis, ITDs are detected by coincidence-sensitive neurons of the medial superior olive (MSO) for which a differential axonal delay from each ear to the MSO compensates for the ITDs. The origin and development of these delays remain poorly understood. To this end, we made recordings from bushy cells (BCs), which project to both MSOs, in adult and in 2-4 week old Mongolian gerbils. First spike latency revealed a frequency-dependent delay likely originating in the cochlea. Latencies were markedly larger for pure tone stimulation than for complex sounds. Combined with our published recordings from the MSO, we observed a developmental decrease in most delays, including the contralateral BC-to-MSO axonal delay. Unexpectedly, the ipsilateral BC-to-MSO axonal delay did not decrease. Anatomical brainstem reconstructions revealed that the inter-MSO distance was stable whereas the cochlear nucleus-to-MSO distance increased during development. Together, this indicated an increase in axonal propagation velocity, particularly for the contralateral projection. The variability in the averaged firing onset between pairs of BCs was found to be as large as the variance in bITDs, suggesting that BCs with matching firing onset are selected to converge onto the same MSO neuron. Together, our results indicate that the developmental speedup of ear-to-MSO delays contributes greatly to bringing the bITDs within their ecological range, but that the difference in path length is not entirely overcome, keeping the ITD tuning biased to contralateral sound sources. Significance statement Humans determine the spatial origin of sounds by comparing their arrival time at either ear. Medial superior olive (MSO) neurons read out these sub-millisecond differences, despite responding ∼7 ms after sound onset. How such remarkable precision is achieved remains unanswered. We dissected the sources of delay and timing variability along the pathway from ear to MSO. Even though the contralateral axonal delay travel speeds up more than the ipsilateral during development, MSO responses remained biased toward contralateral sounds. While classical models emphasize axonal delays as the source of internal timing differences, large variability arises before signals reach the MSO-projecting axons, which necessitates a developmental selection mechanism to overcome this variability and improve the sharpness of ITD tuning.

Standard hearing tests miss cochlear neural degeneration (CND), the loss of synapses between inner hair cells and auditory nerve fibers that may underlie unexplained hearing difficulty in roughly one in ten adults. Envelope following responses (EFRs) can index this neural loss noninvasively, but conventional protocols are too slow for clinical use. We tested a dynamic amplitude-modulated (dAM) EFR that sweeps the full modulation spectrum in a single brief stimulus. In Mongolian gerbils with histologically verified CND, dAM EFRs revealed selective deficits at fast modulation rates without threshold elevation. A machine-learning classifier distinguished young from middle-aged animals with high

The inferior colliculus (IC) is a major midbrain convergence site critical for processing complex sounds and undergoes fundamental changes with age-related hearing loss (ARHL). Local field potentials (LFPs) represent pre-synaptic integration of excitatory and inhibitory signals in local neural populations. Here, we assessed age-related changes in sound-evoked IC LFPs in the CBA/CaJ mouse model of ARHL across the tonotopic axis. We recorded from 495 sites across four age groups (young: 4-6 months; middle: 8-14 months; old: 24-25 months; “oldest old”: 27-31 months), examining LFP responses from dorsal (low-frequency), medial (mid-frequency), and ventral (high-frequency) IC regions. Analysis of the onset depolarization (N1 component) in response to broadband noise bursts revealed significant age-related hyperexcitability in medial and dorsal regions, with oldest old animals showing enhanced responses while ventral regions were unaffected. Amplitude-intensity functions demonstrated significant age × level interactions across all regions, with oldest old animals exhibiting level-dependent hyperexcitability most pronounced at suprathreshold intensities. Time-frequency analysis of LFP spectral content (30-100 Hz) revealed a crossover pattern across medial and dorsal regions, with oldest old animals showing reduced power at low-to-moderate stimulus levels but enhanced power at high stimulus levels. Ventral regions showed a low-level reduction without suprathreshold enhancement. These findings reveal paradoxical enhancement of neural activity in the aging IC, with the most pronounced changes in dorsal and medial regions rather than ventral regions most affected by peripheral hearing loss, suggesting that central hyperexcitability depends on residual afferent drive and implicating region-specific alterations in excitatory-inhibitory balance underlying central presbycusis.