Cell-specific Synaptic Plasticity in the Auditory Brainstem

听觉脑干中的细胞特异性突触可塑性

• 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
• 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

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）：我们先前在背侧耳蜗核（DCN）的研究是一种听觉的脑干核，它发现了在最早的感觉处理水平上发生的新型突触可塑性。我们的长期目标是确定过去的经验如何塑造网络功能以及传入的感官信息的表示。我们应用的目的是确定活动兴奋性和抑制性输入对听觉脑干的突触强度变化的机制和突触规则。该应用的中心假设是，在DCN中，突触上的长期突触可相反形式的长期突触可塑性的协同操作决定了输出单元的激活和尖峰时序精度。在第一个目标中，我们将确定信号传导机制及其相互作用，以塑造DCN上观察到的独特可塑性类型。在AIM 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的突触可塑性的能力。在AIM 3中，我们将确定不同形式的突触可塑性对输出电池的尖峰时序精度的综合作用。了解活动依赖性可塑性在塑造DCN电路活性中的机制和作用不仅应有助于对神经反应的产生产生统一的理解，而且还将对我们的理解和对神经可塑性机械的理解和治疗产生重大影响，包括细胞核，促成性，低言语，超级言论，年龄段，效果，并促进了年龄段，并促进了人们的言论。