Dendritic integration and synaptic plasticity in the MSO

MSO 中的树突整合和突触可塑性

• 批准号: 6809411
• 负责人: Nace L Golding
• 金额: $ 31.65万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6809411
• 关键词: action potentials; auditory pathways; axon; binaural hearing; biophysics; calcium flux; calcium indicator; cell biology; dendrites; developmental neurobiology; gerbil /jird; membrane channels; neural information processing; neural plasticity; olivary body; sectioning; sound frequency; sound perception; synapses; tissue /cell preparation; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): Time-varying features of sound are critical cues that humans and other mammals use to not only understand speech and other communication signals, but to localize sounds as well. The long-term goal of this research is to understand the factors that shape the physiology and development of the auditory circuits underlying these functions. This information is critical not only for understanding the neurobiological basis of human hearing, but also for the development of behavioral strategies that address communication disorders of the central nervous system. This proposal focuses on the medial superior olive (MSO), a major ascending auditory pathway in the brainstem that conveys information about the temporal structure and location of low-frequency sounds. The projecting neurons of the MSO detect the sub millisecond temporal disparities in the arrival of sounds to the two ears, and transmit these cues to higher auditory centers. Within each MSO neuron, the decision whether or not to signal depends on the integration of synaptic inputs in the dendrites, the narrow, branched structures that receive the majority of synaptic input. Despite the pivotal position of the dendrites in processing binaural information, their function remains uninvestigated, due to the technical difficulty of recording electrical activity directly from these small structures. The present study will combine dendritic patch-clamp recordings with calcium imaging in brain slices to examine for the first time dendritic integration in a central auditory neuron. First, experiments will test the hypothesis that voltage-gated channels shape the responses of MSO principal neurons to sub threshold synaptic activity as well as the initiation and propagation of action potentials. Second, we will explore the hypothesis that the strength of synaptic connections to MSO neurons is plastic during development, and regulated by the intrinsic ion channels in the neuron. Finally, experiments will pursue the hypothesis that intracellular calcium influx is the cellular mechanism that links the activity of intrinsic voltage- and ligandgated channels with subsequent changes in synaptic strength. These changes in synaptic strength likely underlie the formation of behaviorally appropriate connections during development, and might represent a form of auditory learning at a low level of the central auditory system.

描述(申请人提供)：声音的时变特征是人类和其他哺乳动物不仅用来理解语音和其他交流信号，而且还用来定位声音的关键线索。这项研究的长期目标是了解影响这些功能的听觉回路的生理和发育的因素。这些信息不仅对于理解人类听力的神经生物学基础至关重要，而且对于开发解决中枢神经系统沟通障碍的行为策略也至关重要。 这一建议的重点是内侧上橄榄(MSO)，这是脑干中的一条主要的上升听觉通路，传达有关低频声音的时间结构和位置的信息。MSO的投射神经元检测声音到达两只耳朵的亚毫秒时间差异，并将这些线索传输到更高的听觉中心。在每个MSO神经元中，是否发出信号取决于突触输入在树突中的整合，树突是接受大部分突触输入的狭窄的分支结构。尽管树突在处理双耳信息中的关键位置，但由于直接从这些小结构记录电活动的技术困难，它们的功能仍未被研究。 这项研究将结合树突状膜片钳记录和脑片上的钙成像，首次检测中枢听神经元中的树突状整合。首先，实验将验证电压门控通道塑造MSO主神经元对阈值下突触活动的反应以及动作电位的启动和传播的假设。其次，我们将探索一种假设，即在发育过程中，与MSO神经元的突触连接的强度是可塑性的，并受到神经元内固有离子通道的调节。最后，实验将继续这一假设，即细胞内钙内流是将固有电压和配基门控通道的活动与随后突触强度变化联系起来的细胞机制。突触强度的这些变化可能是在发育过程中形成行为上适当的联系的基础，也可能代表着中枢听觉系统较低水平的听觉学习的一种形式。