Cortical neuromodulatory mechanisms underlying adaptation and plasticity

适应和可塑性的皮质神经调节机制

基本信息

批准号：
10794638
负责人：
Thanos Tzounopoulos
金额：
$ 58.43万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-18 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10794638
关键词：
Acoustic Nerve Alzheimer&apos s Disease Area Behavior Behavior assessment Behavioral Assay Brain Brain Stem Brain region Cells Chelating Agents Cochlear Implants Detection Development Discrimination Disease Electrophysiology (science)Environment Epilepsy Genes Glutamates Health Hearing Hearing Aids Human Hyperacusis In Vitro Judgment Knock-out Knockout Mice Light Link LoxP-flanked allele Maintenance Mission Modality Mus N-Methyl-D-Aspartate Receptors Neuromodulator Neurons Outcome Pathologic Peripheral Pharmacotherapy Process Recovery Rehabilitation therapy Research Role SLC30A3 gene Schizophrenia Sensory Signal Transduction Specificity Synapses Synaptic Transmission Synaptic plasticity System Tamoxifen Testing Time Tinnitus Transgenic Mice United States National Institutes of Health Zinc auditory rehabilitation autism spectrum disorder awake cell type disability experimental study flexibility gamma-Aminobutyric Acid hearing impairment improved in vivo in vivo calcium imaging inducible Cre knockout gene neuroadaptation neuroregulation noise trauma novel novel strategies pain processing pharmacologic programs recombinase response sensory stimulus sound statistics synaptic function tool zinc-binding protein

项目摘要

PROJECT SUMMARY During our previous studies, we established synaptic zinc as a powerful neuromodulator of synaptic transmission, synaptic plasticity, and sound processing. Based on these findings and our preliminary results, we propose that cortical synaptic zinc is a crucial neuromodulator for cortical adaptation and plasticity (recovery) after noise trauma (peripheral damage). Namely, we plan to answer two main questions: 1) What are the cell- type-specific zincergic neuromodulatory mechanisms underlying cortical adaptation to different background sound statistics? And 2) How do cell-type-specific zincergic neuromodulatory mechanisms contribute to cortical and perceptual recovery after peripheral damage? Answering these questions will advance the field to a new level of understanding about cortical neuromodulatory mechanisms during normal and pathological sensory processing, and create a new framework for approaching and interpreting cortical adaptation and plasticity. Importantly, our proposed studies hold the potential to highlight novel strategies for enhancing hearing after hearing loss, and for mitigating disorders that are associated with maladaptive central plasticity after peripheral damage, such as hyperacusis and tinnitus

项目摘要在先前的研究中，我们建立了突触锌作为突触的强大神经调节剂传输，突触可塑性和声音处理。基于这些发现和我们的初步结果，我们提出皮质突触锌是一种至关重要的神经调节剂，用于皮质适应和可塑性（恢复）噪声创伤后（周围损伤）。即，我们计划回答两个主要问题：1）细胞是什么类型特异性的锌神经调节机制是皮质适应不同背景的基础的合理的统计数据？ 2）细胞型特异性锌神经调节机制如何有助于皮质和外围伤害后的感知恢复？回答这些问题将使该领域成为新的对正常和病理感觉期间皮质神经调节机制的理解水平处理，并创建一个新的框架，以接近和解释皮质适应和可塑性。重要的是，我们提出的研究具有强调增强听力的新型策略的潜力听力损失，以及与外周后与适应不良中心可塑性相关的缓解疾病损坏，例如超源和耳鸣