Biology subjects

Suthakar, K.

Publications and source records attributed to Suthakar, K..

3 recordsLinked to original sources

bioRxiv2025

Age-Related Changes to Olivocochlear Efferent Neurons in Mice with Pathological Hearing

One of the fundamental features of age-related hearing loss (ARHL) is difficulty discriminating speech signals from background noise. In addition to protecting the ear from acoustic trauma, olivocochlear (OC) efferent neurons participate in signal discrimination by virtue of their inhibitory actions on auditory nerve firing. Given the time course of peripheral degeneration in ARHL, we sought to investigate the central degeneration of medial (MOC) and lateral (LOC) efferent neurons in mutant mice that exhibit genetic hearing loss or deafness at different ages. Tests of cochlear function were combined with anatomical and morphological quantification of changes to somatic number, morphology, and location of OC neurons. Neuronal tract tracing methods were employed to label OC neurons in 1-, 3-, and 6-month-old CBA/CaH mice with normal hearing; DBA/2J mice with progressive, high frequency hearing loss; and homozygous Shaker2 mice with congenital deafness. Deaf Shaker2-/- animals exhibited age-related atrophy and loss of MOCs, with contralateral MOCs more affected than ipsilateral MOCs, while LOCs were largely unaffected. No such OC degeneration was observed in DBA/2J mice, even after progressive elevation of low frequency auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE) thresholds. Thus, OC efferent neurons can appear morphologically normal in the complete absence of acoustic input in early life (as in deaf Shaker2-/- animals) and that the retention of these neurons is not affected by late onset high-frequency hearing loss observed in DBA/2J animals. Differential patterns of MOC neuron degeneration may affect functional plasticity of auditory brainstem feedback circuitry in ARHL.

neuroscience↗

bioRxiv2024

ABRpresto: An algorithm for automatic thresholding of the Auditory Brainstem Response using resampled cross-correlation across subaverages

The auditory brainstem response (ABR) is an essential diagnostic indicator of overall cochlear health, used extensively in both basic research and clinical studies. A key quantification of the ABR is threshold, the lowest sound level that elicits a response. Because the morphology of ABR waveforms shift with stimulus level and the overall signal-to-noise ratio is low, threshold estimation is not straightforward. Although several algorithmic approaches have been proposed, the current standard practice remains the visual evaluation of ABR waveforms as a function of stimulus level. We developed an algorithm based on the cross-correlation of two independent averages of responses to the same stimulus. For each stimulus level, the individual responses to each tone-pip are randomly split into two groups. The median waveform for each group is calculated, and then the normalized cross-correlation between these median waveforms is obtained. This process is repeated 500 times to obtain a resampled cross-correlation distribution. For each frequency, the mean values of these distributions are computed for each level and fit with a sigmoid or a power law function to estimate the threshold. Algorithmic thresholds demonstrated robust and accurate performance, achieving 92% accuracy within {+/-}10 dB of human-rated thresholds on a large pool of mouse data. This performance was better than that of several published algorithms on the same dataset. This algorithm has now fully replaced the manual estimation of ABR thresholds for our preclinical studies, thereby saving significant time and enhancing objectivity in the process.

physiology↗

bioRxiv2022

Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage through unclear mechanisms. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize OCNs during postnatal development and after sound exposure. We identified markers for known OCN subtypes, medial (MOC) and lateral (LOC) OCNs, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.

neuroscience↗