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: 7755033
• 负责人: Thanos Tzounopoulos
• 金额: $ 38.41万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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/7755033
• 关键词: Affect; Auditory; Biological Assay; Biological Neural Networks; Brain Stem; CNR1 gene; Cell Nucleus; Cell Shape; Cells; Characteristics; Cues; Data; Dependence; Disease; Electron Microscopy; Endocannabinoids; Equilibrium; Exhibits; Frequencies; Fusiform Cell; Generations; Glutamates; Goals; Hypersensitivity; Interneurons; Learning; Mediating; Metabolic Pathway; Modeling; Monitor; Neuronal Plasticity; Neurons; Outcome; Output; Pattern; Presbycusis; Principal Investigator; Process; Property; Publishing; 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; dorsal cochlear nucleus; experience; interest; neural circuit; novel; operation; postsynaptic; programs; relating to nervous system; response; sensory gating; sensory integration; sensory stimulus; 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）：我们先前在耳蜗背核（DCN）（一种听觉脑干核）中的研究已经发现了在感觉处理的最早阶段发生的突触可塑性的新形式。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征。我们的应用程序的目的是确定机制和突触规则的活动依赖性变化的兴奋性和抑制性输入的听觉脑干的突触强度。本申请的中心假设是，在DCN中的不同细胞类型上的突触处的长期突触可塑性的相反形式的协同操作确定输出细胞的激活和尖峰定时精度。在第一个目标中，我们将确定信号传导机制及其在塑造DCN上观察到的独特可塑性类型方面的相互作用。在目标2中，我们将研究内源性大麻素信号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的尖峰定时精度的综合影响。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对神经反应产生的统一理解，而且还将对我们理解和治疗由神经可塑性机制引起的疾病产生重大影响，包括耳鸣，超敏反应，听觉过敏，年龄相关性听力损失和言语辨别力受损。