Cortical neuromodulatory mechanisms underlying adaptation and plasticity

适应和可塑性的皮质神经调节机制

• 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
• 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' 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

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

项目概要 在我们之前的研究中，我们确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。根据这些发现和我们的初步结果，我们 提出皮质突触锌是皮质适应和可塑性（恢复）的关键神经调节剂 噪音创伤（外周损伤）后。也就是说，我们计划回答两个主要问题：1）什么是细胞- 皮层适应不同背景的类型特异性锌能神经调节机制 健全的统计数据？ 2) 细胞类型特异性锌能神经调节机制如何促进皮质 以及外周损伤后的知觉恢复？回答这些问题将把该领域推进到一个新的阶段 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来接近和解释皮质适应和可塑性。 重要的是，我们提出的研究有可能强调术后增强听力的新策略 听力损失，以及缓解与周围环境适应不良中枢可塑性相关的疾病 损伤，例如听觉过敏和耳鸣