# Mechanisms of Growth Factor Responsiveness in the Aging Auditory System > **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2020 · $543,659 ## Abstract Abstract: During hearing development, auditory neurons are wired correctly, both qualitatively and quantitatively, with specific types of spiral ganglion neurons (SGN; auditory afferents) and cochlear nucleus (CN) nerve fibers. Maturation of the auditory neural pathway ensues along the functional tonotopic frequency axis, apparently correlating with time and space/location-dependent gradients in neurotrophins (NTs). In addition, the SGNs develop cochleotopic responses to sound and achieve cochleotopic projections to the cochlear nuclei (CN). The activity of SGNs maintains the number, size and functions of cells in the CN. Previous studies suggest that this process is regulated in part by neurotrophic factors (e.g. brain-derived neurotrophic factor (BDNF)). Expression data show that BDNF expression undergo developmental and age-dependent shifts in their cellular and longitudinal patterns of expression in the auditory pathway. This pattern was proposed to dictate distinct apico- basal function of auditory neuron electrical properties, in turn requirements for cochleotopic and central auditory neuron fine tuning. Despite the appeal of the NT-gradient and age-dependent hypothesis for auditory neural properties, this idea rests on correlative evidence, disputed by some. We seek to unequivocally test and clarify the NT-gradient predictions, and to understand BDNF-mediated auditory functional plasticity and how it sculpts age-related hearing loss (ARHL). We hypothesize that gradual decline in BDNF signaling is one of the common cause for ARHL. We will unravel the function of BDNF in auditory neuronal plasticity using well-characterized cre lines (e.g. Rosa26-creER; Fgf8-cre, Atoh1-cre) to selectively reduce or eliminate BDNF in floxed lines, to study the long- term influence of BDNF levels on auditory signal processing in aging mice. In Aim 1, we will quantify BDNF signaling expression in the auditory system, determine the source/s and the ensuing age-related changes in the auditory neural pathway. Single molecule fluorescent in situ hybridization (SmFISH) and immunocytochemical techniques will be used to quantify mRNA and protein expression and the age-related changes of BDNF. Additionally, age-related changes in BDNF-receptors expression will be quantified. In Aim 2, we will determine BDNF-mediated auditory plasticity with partial or delayed loss of BDNF. These goals will be accomplished using inducible cre lines (e.g. Rosa26-creER) to eliminate all BDNF at various stages of aging from ~3-week to 2-year old mice. We will determine the age-related cellular properties of auditory neurons (e.g. SGNs). Finally, in Aim 3, we will identify BDNF-mediated neural and synaptic plasticity with partial and delayed loss of BDNF. We will use the animal models outlined in Aim 2 to identify changes in synaptic function at the calyx of Held, due to BDNF loss/decline. This central auditory synapse, originates in the ventral cochlear nucleus (VCN), and project contra... ## Key facts - **NIH application ID:** 9896749 - **Project number:** 5R01AG060504-03 - **Recipient organization:** UNIVERSITY OF NEVADA RENO - **Principal Investigator:** BERND FRITZSCH - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $543,659 - **Award type:** 5 - **Project period:** 2018-08-15 → 2023-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9896749 ## Citation > US National Institutes of Health, RePORTER application 9896749, Mechanisms of Growth Factor Responsiveness in the Aging Auditory System (5R01AG060504-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896749. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*