NSF-IOS-BSF:Influence of neuronal zinc homeostasis on cortical responses to sound

NSF-IOS-BSF：神经元锌稳态对皮质对声音反应的影响

基本信息

批准号：
1655480
负责人：
Elias Aizenman
金额：
$ 124万
依托单位：
University of Pittsburgh
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2023-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1655480&HistoricalAwards=false
关键词：
NSF IOS BSF Influence neuronal

项目摘要

In the auditory system, as sound properties of the auditory environment change, auditory cells in the brain adjust their dynamic range of their responses to match changing background noise. This type of adaptation to sound is extremely important for brain auditory processing, for it provides a mechanism for allowing us to focus on specific sounds in the presence of variable background sound levels. However, the mechanisms underlying this adaptation remain unknown. This project will establish a previously unknown link between the metal zinc in the brain and control of auditory processing in the cerebral cortex of the brain. Thus, findings from this project will advance understanding about mechanisms of adaptations of sound processing and create a new framework for approaching and interpreting the role of the auditory system in the processing of sound. This joint NSF/BSF project will establish a joint US-Israel student exchange program as well as target underserved student populations both in Israel and the US and train them in problem-solving at behavioral, neural and molecular levels of analysis. Broad dissemination of the work will be made possible by active engagement with the International Society for Zinc Biology through a variety of activities.Zinc is packaged into glutamatergic vesicles by the ZnT3 zinc transporter, and released from synaptic terminals in an activity-dependent manner. Although the basic principles underlying zinc neurotransmission have begun to be deciphered, the sensory stimuli leading to the modulation of zinc signaling as well as the role of zinc in regulating sensory processing remain unknown. The central hypothesis of this project is that sound dependent changes in zinc signaling in the auditory cortex play a role in the sound level adaptation of neuronal input-output functions to match the prevailing stimulus intensity of the acoustic environment. This project aims to: i. Identify the consequences of experience-dependent plasticity of zinc-mediated modulation on input-output functions and receptive fields of layers 2/3 auditory cortical neurons in vivo, and ii. Establish the cellular and molecular mechanisms mediating the experience-dependent alterations in zinc-dependent auditory cortical processing. These studies will thus provide the first analysis of regulation of neuronal zinc and its effects on auditory processing, at the molecular, cellular and systems levels.

在听觉系统中，随着听觉环境的声音属性的变化，大脑中的听觉细胞会调整其响应的动态范围，以匹配不断变化的背景噪声。这种对声音的适应对于大脑听觉处理非常重要，因为它提供了一种机制，可以使我们能够在存在可变背景声音级别的情况下专注于特定的声音。但是，这种适应的基础机制仍然未知。该项目将在大脑中的金属锌与大脑大脑皮层中听觉加工的控制之间建立以前未知的联系。因此，该项目的发现将提高人们对声音处理适应机制的理解，并创建一个新的框架，以接近和解释听觉系统在声音处理中的作用。该联合NSF/BSF项目将建立一个以色列联合学生交流计划，以及在以色列和美国的目标学生人数不足，并在行为，神经和分子分析水平的问题上解决问题。通过各种活动与国际锌生物学学会积极互动，将使工作的广泛传播成为可能。Zinc通过ZNT3锌转运蛋白将Zinc包装到谷氨酸能囊泡中，并以活动依赖性方式从突触终端释放。尽管已经开始解密了锌神经传递的基本原理，但感官刺激导致锌信号的调节以及锌在调节感觉处理中的作用仍然未知。该项目的中心假设是，听觉皮层中锌信号的声音变化在神经元输入输出函数的声音适应中起作用，以匹配声学环境的普遍刺激强度。该项目的目的是：i。确定锌介导的调制的经验依赖性可塑性对体内2/3听觉皮层神经元的输入输出功能和接受场的后果。建立介导锌依赖性听觉皮质加工经验依赖性改变的细胞和分子机制。因此，这些研究将提供对神经元锌调节及其对分子，细胞和系统水平上听觉加工的影响的首次分析。