SK2 channels are required for function and long-term survival of efferent synapses on mammalian outer hair cells

Cochlear hair cells use SK2 currents to shape responses to cholinergic efferent feedback from the brain. Using SK2-/- mice, we demonstrate that, in addition to their previously defined role in modulating hair cell membrane potentials, SK2 channels are necessary for long-term survival of olivocochlear fibers and synapses. Loss of the SK2 gene also results in loss of electrically driven olivocochlear effects in vivo, and down regulation of ryanodine receptors involved in calcium-induced calcium release, the main inducer of nAChR evoked SK2 activity. Generation of double-null mice lacking both the α10 nAChR gene, loss of which results in hypertrophied olivocochlear terminals, and the SK2 gene, recapitulates the SK2-/- synaptic phenotype and gene expression, and also leads to down regulation of α9 nAChR gene expression. The data suggest a hierarchy of activity necessary to maintain early olivocochlear synapses at their targets, with SK2 serving an epistatic, upstream, role to the nAChRs.Fil: Murthy, Vidya. Tufts University; Estados UnidosFil: Maison, Stéphane F.. Massachusetts Eye and Ear Infirmary; Estados Unidos. Harvard Medical School; Estados UnidosFil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University; Estados UnidosFil: Haque, Nadeem. University of Notre Dame; Estados UnidosFil: Bond, Chris T.. Oregon Health Sciences University; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Adelman, John P.. Oregon Health Sciences University; Estados UnidosFil: Liberman, M. Charles. Massachusetts Eye and Ear Infirmary; Estados Unidos. Harvard Medical School; Estados UnidosFil: Vetter, Douglas E.. Tufts University; Estados Unido

Individual differences in supra-threshold auditory perception - mechanisms and objective correlates

Thesis (Ph.D.)--Boston UniversityTo extract content and meaning from a single source of sound in a quiet background, the auditory system can use a small subset of a very redundant set of spectral and temporal features. In stark contrast, communication in a complex, crowded scene places enormous demands on the auditory system. Spectrotemporal overlap between sounds reduces modulations in the signals at the ears and causes masking, with problems exacerbated by reverberation. Consistent with this idea, many patients seeking audiological treatment seek help precisely because they notice difficulties in environments requiring auditory selective attention. In the laboratory, even listeners with normal hearing thresholds exhibit vast differences in the ability to selectively attend to a target. Understanding the mechanisms causing these supra-threshold differences, the focus of this thesis, may enable research that leads to advances in treating communication disorders that affect an estimated one in five Americans. Converging evidence from human and animal studies points to one potential source of these individual differences: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Electrophysiological measures of sound encoding by the auditory brainstem in humans and animals support the idea that the temporal precision of the early auditory neural representation can be poor even when hearing thresholds are normal. Concomitantly, animal studies show that noise exposure and early aging can cause a loss (cochlear neuropathy) of a large percentage of the afferent population of auditory nerve fibers innervating the cochlear hair cells without any significant change in measured audiograms. Using behavioral, otoacoustic and electrophysiological measures in conjunction with computational models of sound processing by the auditory periphery and brainstem, a detailed examination of temporal coding of supra-threshold sound is carried out, focusing on characterizing and understanding individual differences in listeners with normal hearing thresholds and normal cochlear mechanical function. Results support the hypothesis that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests as deficits both behaviorally and in subcortical electrophysiological measures in humans. Based on these results, electrophysiological measures are developed that may yield sensitive, fast, objective measures of supra-threshold coding deficits that arise as a result of cochlear neuropathy

Bioinspired microstructured adhesives for medical applications

Adhesives for interaction with human skin and tissues are needed for multiple applications, from wearable electronics to medical devices for diagnostics and therapy. Bioinspired fibrillar structures, initially developed for robotics, were upgraded for adhesion to biological surfaces to solve problems in medicine. Using a fibrillar array topped by a soft skin adhesive (SSA) layer, the film-terminated design exhibits effective adhesion to skin-like rough surfaces compared to unstructured samples. The glue-free, reliable adhesion to skin opens a large spectrum of possibilities for applications in biomedicine. Moreover, we investigated the adhesion of the microstructure to explanted mouse eardrums for application as wound dressing for eardrum perforations. The subsurface microstructure was also found to dampen any impact, protecting the sensitive membrane during application. Animal tests showed promising results to replace current surgical approaches with a less invasive and more effective treatment with microstructured adhesives.Adhäsive für die Interaktion mit menschlicher Haut und menschlichem Gewebe werden für zahlreiche Anwendungen, von Wearables bis zu medizinischen Geräten für Diagnostik und Therapie, benötigt. Bioinspirierte fibrilläre Mikrostrukturen, die ursprünglich für die Robotik entwickelt wurden, wurden hier für die Haftung an biologischen Oberflächen weiterentwickelt, um innovative Anwendungen in der Medizin zu bieten. Unter Verwendung eines fibrillären Arrays, das mit einer Schicht aus einem weichem Polymer (SSA) bedeckt ist, zeigt das filmterminierte Design, im Vergleich zu unstrukturierten Proben, eine effektive Haftung auf hautähnlichen rauen Oberflächen. Die klebstofffreie, zuverlässige Haftung auf der Haut eröffnet ein breites Spektrum an Verwendungsmöglichkeiten in der Biomedizin. Darüber hinaus untersuchten wir die Haftung der Mikrostruktur an explantierten Maus-Trommelfellen zur Anwendung als Verschlussmaterial bei Trommelfellperforationen. Es wurde auch festgestellt, dass die Mikrostruktur unter der Deckschicht zusätzlichen Druck dämpft und die empfindliche Membran während der Applikation schützt. Tierversuche zeigten vielversprechende Ergebnisse zum Ersatz aktueller chirurgischer Eingriffe durch eine weniger invasive und effektivere Behandlung mit mikrostrukturierten Pflastern

Wireless earbuds for low-cost hearing screening

We present the first wireless earbud hardware that can perform hearing screening by detecting otoacoustic emissions. The conventional wisdom has been that detecting otoacoustic emissions, which are the faint sounds generated by the cochlea, requires sensitive and expensive acoustic hardware. Thus, medical devices for hearing screening cost thousands of dollars and are inaccessible in low and middle income countries. We show that by designing wireless earbuds using low-cost acoustic hardware and combining them with wireless sensing algorithms, we can reliably identify otoacoustic emissions and perform hearing screening. Our algorithms combine frequency modulated chirps with wideband pulses emitted from a low-cost speaker to reliably separate otoacoustic emissions from in-ear reflections and echoes. We conducted a clinical study with 50 ears across two healthcare sites. Our study shows that the low-cost earbuds detect hearing loss with 100% sensitivity and 89.7% specificity, which is comparable to the performance of a $8000 medical device. By developing low-cost and open-source wearable technology, our work may help address global health inequities in hearing screening by democratizing these medical devices