Alterations and mechanisms of auditory information processing in the aging auditory pathway

衰老听觉通路中听觉信息处理的改变和机制

• 批准号: 10496287
• 负责人: Maria Eulalia Rubio
• 金额: $ 41.23万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10496287
• 关键词: Acoustic Nerve; Affect; Age; Aging; Area; Auditory; Auditory area; Auditory system; Axon; Biological Markers; Brain; Brain Stem; CBA/CaJ Mouse; Central Nervous System; Cochlea; Cochlear nucleus; Code; Complex; Data; Degenerative Disorder; Demyelinations; Diameter; Environment; Equilibrium; Exhibits; Fiber; Fluorescent Antibody Technique; Glutamate Receptor; Goals; Hearing problem; Hyperacusis; Impairment; Individual; Joints; Molecular; Monitor; Motor Activity; Myelin; Nerve; Nerve Fibers; Neurons; Optics; Organelles; Outcome; Pathway interactions; Peripheral; Physiological; Physiology; Presbycusis; Presynaptic Terminals; Process; Property; Public Health; Pupil; Pyramidal Tracts; Research Personnel; Sensory; Signal Transduction; Site; Sound Localization; Speech; Structure; Sum; Synapses; Synaptic Transmission; System; Testing; Tinnitus; age related; aged; aging auditory system; aging brain; arm; auditory pathway; auditory stimulus; experimental study; hearing impairment; information processing; innovation; insight; myelination; neural; neuronal excitability; novel; postsynaptic; presynaptic; sound; stem; transmission process

Abstract Age-related hearing loss (ARHL), also referred to as presbycusis, is a complex degenerative disease characterized by hearing impairment. The condition is a significant public health problem, affecting 40% of individuals aged between 55 and 74. ARHL is attributed to central and peripheral auditory system degeneration. Central ARHL refers to age-associated degeneration in the auditory portion of the central nervous system, which affects the ability to localize the temporal and spatial origins of sounds and impairs speech understanding in noisy environments. However, studies so far have not fully elucidated the cellular mechanisms underlying deficits to temporal precision of sound localization and speech understanding in aging. In Aim 1, we will determine the age-dependent structural and molecular remodeling of central auditory synapses. We hypothesize that aging alters key structural and molecular parameters at the central synapses. As a result, the endbulb and calyx of Held synapses exhibit decreased activity. Studies in Aim 2 will determine the age-dependent structural and molecular remodeling of central nerve axonal fibers. We hypothesize that age-related deficits in myelin and internode distance along the auditory nerve and calyx axonal fibers will decrease conduction velocity (CV) and degrade synaptic activity. In addition, another most notable change in ARHL is an increase in neuronal excitability. The degradation of input at the auditory neural axis periphery shifts the balance of excitation and inhibition throughout the auditory hierarchy, including the cochlear nucleus (CN), superior olivary complex (SOC), and auditory cortex (ACtx). It leads to altered neuronal excitability and auditory dysfunctions, including tinnitus and hyperacusis. Although altered neuronal excitability (“hypo-” or “hyper”-excitability) has been found in several brain stations in the ascending auditory hierarchy, its presence in descending systems is less understood. We hypothesize that the mechanism of altered age-related neuronal excitability in the ACtx stems from modified CN and SOC pre- and post-synaptic properties, as well as neuronal demyelination. In Aim 3, we will identify structural changes in pyramidal tract (PT) projection pathways in the aging brain. We hypothesize that aging incurs structural plasticity in PT projection neurons' downstream targets. Studies in Aim 4 will determine sensory processing deficits in PT projection pathways in the aging brain. We hypothesize that altered excitability in the aged auditory system systematically degrades the spectrotemporal processing of sound. The overall goal in this project (P3) is to understand the age-dependent structural and molecular remodeling of central auditory synapses and central nerve axonal fibers, as well as providing novel insights into how aging influences structural plasticity throughout the auditory system and how connectivity with downstream brain areas are altered in aging.

摘要