Cell-specific Synaptic Plasticity in the Auditory Brainstem

听觉脑干中的细胞特异性突触可塑性

基本信息

批准号：
7258254
负责人：
Thanos Tzounopoulos
金额：
$ 30.79万
依托单位：
ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-08 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7258254
关键词：
Affect Auditory Biological Assay Biological Neural Networks Brain Stem CNR1 gene Cell Nucleus Cell Shape Cells Characteristics Chromosome Pairing Cues Data Dependence Disease Electron Microscopy Endocannabinoids Equilibrium Exhibits Fire - disasters Frequencies Fusiform Cell Generations Glutamates Goals Hypersensitivity Interneurons Learning Mediating Metabolic Pathway Modeling Monitor Neuronal Plasticity Neurons Operative Surgical Procedures Outcome Output Pattern Presbycusis Principal Investigator Process Property Publishing Rate Regulation Relative (related person)Role Scheme Sensory Sensory Process Shapes Signal Pathway Signal Transduction Specificity Speech Discrimination Structure Synapses Synaptic plasticity Techniques Time Tinnitus Whole-Cell Recordings Work base calmodulin-dependent protein kinase II cell type computerized data processing concept dorsal cochlear nucleus experience interest neural circuit novel postsynaptic programs relating to nervous system response sensory gating sensory integration sensory stimulus size somatosensory sound ward

项目摘要

DESCRIPTION (provided by applicant): Our previous studies in the dorsal cochlear nucleus (DCN), an auditory brainstem nucleus, have uncovered novel forms of synaptic plasticity that occur at the earliest levels of sensory processing. Our long-term goal is to determine how past experience shapes network function and representations of incoming sensory information. The objective of our application is to determine mechanisms and synaptic rules underlying activity-dependent changes in synaptic strength of excitatory and inhibitory inputs to the auditory brainstem. The central hypothesis of the application is that the concerted operation of opposing forms of long-term synaptic plasticity at synapses onto different cell types in the DCN determines activation and spike timing precision of the output cell. In the first Aim, we will determine the signaling mechanisms and their interactions in shaping the unique types of plasticity observed on the DCN. In Aim 2, we will investigate the synapse- specific expression of endocannabinoid signaling and its ability to determine different types of synaptic plasticity. In Aim 3, we will determine the combined effect of different forms of synaptic plasticity on spike timing precision of the output cell. Understanding the mechanisms and role of activity-dependent plasticity in shaping the activity of the DCN circuitry should not only contribute to a unified understanding of the generation of neural responses, but will also have a significant impact on our understanding and cures for disorders caused by neural plasticity-like mechanisms, including tinnitus, hypersensitivity, hyperacousis, age-related hearing loss, and impaired speech discrimination.

描述（由申请人提供）：我们之前对耳蜗背核（DCN）（听觉脑干核）的研究发现，突触可塑性的新形式发生在感觉处理的最早水平。我们的长期目标是确定过去的经验如何塑造网络功能和传入感官信息的表示。我们应用的目的是确定听觉脑干的兴奋性和抑制性输入的突触强度的活动依赖性变化的机制和突触规则。该应用的中心假设是，DCN 中不同细胞类型的突触处相反形式的长期突触可塑性的协同操作决定了输出细胞的激活和尖峰计时精度。在第一个目标中，我们将确定信号机制及其相互作用，以塑造 DCN 上观察到的独特可塑性类型。在目标 2 中，我们将研究内源性大麻素信号传导的突触特异性表达及其确定不同类型突触可塑性的能力。在目标 3 中，我们将确定不同形式的突触可塑性对输出细胞尖峰计时精度的综合影响。了解活动依赖性可塑性在塑造 DCN 电路活动中的机制和作用不仅有助于统一理解神经反应的产生，而且还将对我们对神经引起的疾病的理解和治疗产生重大影响。可塑性机制，包括耳鸣、过敏、听觉亢进、年龄相关性听力损失和言语辨别能力受损。