Elizabeth
Norris
Tracking the Recovery of Auditory Processing in Deaf Otoferlin-Deficient Mice Following AAV-Mediated Gene Replacement Therapy
Abstract profile. Full document pending author claim.
Authors:
Elizabeth Norris, Kameron Clayton, Daniel Polley
Date Created:
2025-01-01
Course Title:
Professor:
Not specified
About Paper:
In DFNB9, a genetic form of deafness, point mutations in the treatment. Baseline recordings were performed three consecutive otoferlin gene encoding a vesicle-fusion protein block sound days prior to treatment. Auditory brainstem responses (ABRs) transmission to the brain. The emergence of hearing after AAV- were used to measure synchronized neural activity in the auditory mediated gene replacement therapy has been demonstrated in nerve, brainstem, and midbrain, while longer-latency cortical otoferlin-deficient (OTOF ) mice and humans. However, brain auditory evoked potentials (CAEPs) were used to measure sound- plasticity after the cochlea first transmits acoustic signals is noevoked activity in the auditory cortex. well understood. Using a mouse model, our project aims to One hypothesis is that sound-evoked neural activity will increase investigate: if a functioning ear were suddenly connected to an adult brain deprived of auditory input from birth, how and when more rapidly and reach normative levels for later stages of would dormant neural circuits respond, and would normal auditory sound processing, which may retain more plasticity. Preliminary results show that normal CAEPs emerge just two days post- perception be supported? treatment. In contrast, ABRs took one week to emerge, and Chronic recordings of sound-evoked neural activity and reflexive sound-evoked reflexive behaviors emerged over a prolonged time +/+ facial response-/-ere performed in four wild-type OTOF mice course in parallel with ABR measurements. These results suggest and two OTOF mice, before and after gene therapy. To track cortical sound processing can rapidly emerge despite persistent auditory processing at single-day resolution in unanesthetized deficits in subcortical processing. By tracking the emergence of mice, four microwires were implanted atop the brain surface ABRs and CAEPs while simultaneously performing behavioral through small holes in the skull, and an electrode connector assessments, we aim to advance understanding of neural plasticity and headplate were attached to the skull surface. Head-fixed at different auditory processing stages and investigate how early electrocorticography and facial videography recordings were neural encoding translates into auditory perception. performed in treated OTOF -/mice for 21 consecutive days post-
Abstract:
In DFNB9, a genetic form of deafness, point mutations in the treatment. Baseline recordings were performed three consecutive otoferlin gene encoding a vesicle-fusion protein block sound days prior to treatment. Auditory brainstem responses (ABRs) transmission to the brain. The emergence of hearing after AAV- were used to measure synchronized neural activity in the auditory mediated gene replacement therapy has been demonstrated in nerve, brainstem, and midbrain, while longer-latency cortical otoferlin-deficient (OTOF ) mice and humans. However, brain auditory evoked potentials (CAEPs) were used to measure sound- plasticity after the cochlea first transmits acoustic signals is noevoked activity in the auditory cortex. well understood. Using a mouse model, our project aims to One hypothesis is that sound-evoked neural activity will increase investigate: if a functioning ear were suddenly connected to an adult brain deprived of auditory input from birth, how and when more rapidly and reach normative levels for later stages of would dormant neural circuits respond, and would normal auditory sound processing, which may retain more plasticity. Preliminary results show that normal CAEPs emerge just two days post- perception be supported? treatment. In contrast, ABRs took one week to emerge, and Chronic recordings of sound-evoked neural activity and reflexive sound-evoked reflexive behaviors emerged over a prolonged time +/+ facial response-/-ere performed in four wild-type OTOF mice course in parallel with ABR measurements. These results suggest and two OTOF mice, before and after gene therapy. To track cortical sound processing can rapidly emerge despite persistent auditory processing at single-day resolution in unanesthetized deficits in subcortical processing. By tracking the emergence of mice, four microwires were implanted atop the brain surface ABRs and CAEPs while simultaneously performing behavioral through small holes in the skull, and an electrode connector assessments, we aim to advance understanding of neural plasticity and headplate were attached to the skull surface. Head-fixed at different auditory processing stages and investigate how early electrocorticography and facial videography recordings were neural encoding translates into auditory perception. performed in treated OTOF -/mice for 21 consecutive days post-
Source:
Harvard / Harvard College | Pforzheimer House | Neuroscience | 2027 / 2025
Topics:
auditory, sound, processing, mice, neural, gene, brain, activity, otof, otoferlin, therapy, treatment
