Biology subjects

Walton, J. P.

Publications and source records attributed to Walton, J. P..

4 recordsLinked to original sources

bioRxiv2026

Age-related hyperexcitability in the mouse inferior colliculus: evidence from sound-evoked local field potentials

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 x 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.

neuroscience↗

bioRxiv2026

Validating the Gap-Startle Paradigm for Tinnitus Detection: A Machine Learning Approach in CBA/CaJ Mice

Tinnitus is one of the most common hearing disorders affecting one-third of Americans and is defined as the buzzing or ringing sound one perceives in one or both ears in the absence of an acoustic stimulus. One objective method for tinnitus screening in rodents is gap prepulse inhibition of the acoustic startle reflex (GPIAS), a reduction in the abrupt motor response elicited by an intense auditory stimulus following a silent gap in noise. Reduced inhibition by gaps embedded in narrow-band noise is hypothesized to reflect the primary tinnitus pitch, as the tinnitus "fills-in" the gap. However, Lobarinas et al. (2013) identified a critical limitation: after acoustic trauma or hearing loss, rodents often exhibit markedly diminished acoustic startle reflexes, creating a "floor effect" where further suppression becomes undetectable even if gap perception remains intact, leading to false-positive tinnitus screening results. To address this limitation, we utilized the CBA/CaJ mouse model to assess tactile airpuff modification efficacy and employed a machine learning algorithm to classify startle responses, achieving 98% accuracy in differentiating startles from non-startles. We induced unilateral conductive hearing loss via ear plugging and found enhanced gap detection ability, contrasting with false-positive tinnitus indicators observed in rats by Lobarinas and colleagues. We also pharmacologically induced tinnitus via sodium salicylate, revealing frequency-specific alterations in gap detection patterns. Our findings suggest that differences in data analysis methodology, specifically using a machine learning algorithm to filter non-startle responses, may explain species-specific differences between mouse and rat models and significantly improve GPIAS validity as a tinnitus screening assessment tool.

animal behavior and cognition↗

bioRxiv2020

Rescuing auditory temporal processing with a novel augmented acoustic environment in an animal model of congenital hearing loss

Congenital sensorineural hearing loss (SNHL) affects thousands of infants each year and results in significant delays in speech and language development. Previous studies have shown that early exposure to a simple augmented acoustic environment (AAE) can limit the effects of progressive SNHL on hearing sensitivity. However, SNHL is also accompanied by "hidden hearing loss" that is not assessed on standard audiological exams, such as reduced temporal processing acuity. To assess whether sound therapy may improve these hidden deficits, a mouse model of congenital SNHL was exposed to simple or temporally complex AAE. Peripheral function and sound sensitivity in auditory midbrain neurons improved following exposure to both types of AAE. However, only exposure to a novel, temporally complex AAE significantly improved a measure of temporal processing acuity, neural gap-in-noise detection in the auditory midbrain. These experiments suggest that targeted sound therapy may improve hearing outcomes for children suffering from congenital SNHL.

neuroscience↗

bioRxiv2019

A modular microreservoir for active implantable drug delivery

Active implantable microscale reservoir-based drug delivery systems enabled novel and effective drug delivery concepts for both systemic and localized drug delivery applications. These systems typically consist of a drug reservoir and an active pumping mechanism for precise delivery of drugs. Here we present a stand-alone, refillable, scalable, and fully implantable microreservoir platform to be integrated with micropumps as a storing component of active implantable drug delivery microsystems. The microreservoir was fabricated with 3D-printing technology, enabling miniature, scalable, and planar structure, optimized for subcutaneous implantation especially in small animals (e.g., mouse), while being readily scalable for larger animals and human translation. Three different capacities of the microreservoir (1 L, 10 L, and 100 L) were fabricated and characterized all with 3 mm thickness. The microreservoir consists of two main parts: a cavity for long-term drug storage with an outlet microtubing (250 m OD, 125 m ID), and a refill port for transcutaneous refills through a septum. The cavity membrane is fabricated with thin Parylene-C layers using a polyethylene glycol sacrificial layer, minimizing restoring force and hence backflow, as fluid is discharged. This feature enables integration to normally-open mechanisms and improves pumping efficiency when integrated to normally-closed pumps. The results of in vitro optimization and characterization of the cavity membrane show 95% extraction percentage of the cavity with insignificant (2%) backflow due to restoring force of the membrane. The refill port septum thickness is minimized down to 1 mm by a novel pre-compression concept, while capable of ~65000 injections with 30 Ga non-coring needles without leakage under 100 kPa (4x greater than physiological backpressure). To demonstrate integrability of the microreservoir to an active micropump, the 10 L microreservoir was integrated to a micropump recently developed in our laboratory, making an implantable drug delivery microsystem. Two different microsystems were subcutaneously implanted in two mice, and the outlet microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion. The in vivo results show a mean shift of 22.1 dB after 20 min for the most basal region, matching with syringe pump results. A biocompatibility experiment was performed on the microsystem for six months to assess design and fabrication suitability for chronic subcutaneous implantation and clinical translational development. The results demonstrate very favorable signs of biocompatibility for long-term implantation. Although tested here on mice for a specific inner ear application, this low-cost design and fabrication methodology is scalable for use in larger animals and human for different applications/delivery sites.

bioengineering↗