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

项目摘要 在我们之前的研究中，我们确定突触锌是一种强大的突触神经调节剂， 传递、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 提出皮层突触锌是皮层适应性和可塑性（恢复）的重要神经调质 噪声损伤（外周损伤）。也就是说，我们计划回答两个主要问题：1）细胞是什么- 皮层对不同背景适应的类型特异性锌能神经调节机制 健全的统计？和2）细胞类型特异性锌能神经调节机制如何有助于皮质 和知觉恢复的能力吗解决这些问题将使该领域进入一个新的阶段。 对正常和病理感觉过程中皮层神经调节机制的理解水平 处理，并创建一个新的框架，接近和解释皮层适应和可塑性。 重要的是，我们提出的研究有可能突出新的策略，以提高听力后， 听力损失，并用于减轻与周围神经损伤后适应不良的中枢可塑性相关的疾病。 损伤，如听觉过敏和耳鸣