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Corticostriatal Contributions to Auditory Perceptual Hypersensitivity

皮质纹状体对听觉感知超敏反应的贡献

基本信息

批准号：
10163669
负责人：
Matthew McGill
金额：
$ 3.37万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10163669
关键词：
Acoustic Trauma Acoustics Address Aging Animal Model Auditory Auditory area Auditory system Basal Ganglia Behavior Behavioral Calcium Chronic Cochlea Corpus striatum structure Decision Making Development Disease Environment Esthesia Evaluation Frequencies Growth Head Hearing problem High-Frequency Hearing Loss Human Hyperactivity Hyperacusis Hypersensitivity Image Injury Label Lead Lesion Link Loudness Loudness Perception Maps Measures Mentors Motor Mus Neurodevelopmental Disorder Neurologic Neurons Noise Noise-Induced Hearing Loss Opsin Pain Threshold Pathology Peripheral Peripheral Nerves Persons Phenotype Population Prevalence Probability Process Proxy Recording of previous events Reflex action Reporting Reproducibility Retina Rewards Sensory Sensory Disorders Stimulus System Techniques Testing Time Training Viral Visual autism spectrum disorder base behavior measurement cell type deprivation driving force excitatory neuron hearing impairment insight nervous system disorder neural circuit normal hearing optogenetics relating to nervous system response sensory cortex sensory input sensory stimulus sensory system somatosensory sound training project two-photon

项目摘要

Project Summary/Abstract Across sensory systems, a deprivation of peripheral input is associated with a compensatory increase in neural excitability at the level of sensory cortex. Commonly, this compensatory process overshoots the mark, resulting in hyperactivity along with perceptual hypersensitivity to sensory stimuli. Such observations have a long history in the auditory system: noise-induced damage to the cochlea is associated with a paradoxical cortical hyperactivity and perceptual abnormalities such as hyperacusis, an auditory disorder characterized by an increase in perceived loudness to moderately intense sounds. Although it is believed that cortical hyperactivity is a driving force behind perceptual hypersensitivity, a definitive link is yet unclear. This mentored training project will combine chronic behavioral, two-photon imaging, and optogenetics techniques in mice to understand the neural changes underlying the emergence of a behavioral hypersensitivity phenotype following a high frequency noise-induced hearing loss. Studies pursuant to Aim 1 will develop a two-alternative forced choice task that assesses loudness perception in head-fixed mice. Such a behavior provides two major advances: i) direct evaluation of perceptual hypersensitivity after noise exposure, and ii) the ability to do chronic imaging in behaving mice. Studies in Aim 2 will use chronic two-photon calcium imaging of auditory corticostriatal neurons, a defined cell type directly relevant to auditory-guided behavior. Imaging will take place in both passive and task-engaged conditions both to allow full characterization of frequency and intensity response changes across the tonotopic map and to enable direct comparison of neural activity changes with perceptual decision-making. Aim 3 will test the hypothesis that inducing auditory corticostriatal hyperexcitability in unexposed control mice with healthy cochleae is sufficient to increase the probability of perceptually categorizing moderately intense sounds as loud. Corticostriatal neurons will be shifted in and out of hyperactive states using stabilized step function opsins to temporarily induce stable and reversible planes of hyperexcitability in normal, behaving mice. Altogether, this project will overcome previous technical limitations to gain a more complete understanding of the neural circuit pathology underlying auditory perceptual hypersensitivity. Beyond peripheral injury, sensory hypersensitivity is associated with other conditions such as aging and neurodevelopmental disorders including autism. Thus, insight from this project into the neural signatures of hyperactivity and behavioral hypersensitivity will prove valuable broadly for hearing impairment, other sensory disorders, and related neurological conditions.

项目总结/文摘