Dendritic integration and synaptic plasticity in the MSO

MSO 中的树突整合和突触可塑性

• 批准号: 7057812
• 负责人: Nace L Golding
• 金额: $ 32.68万
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057812
• 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（由申请人提供）：声音的时变特征是人类和其他哺乳动物使用的关键提示，不仅可以理解语音和其他交流信号，还可以定位声音。这项研究的长期目标是了解塑造这些功能背后的听觉电路生理和发展的因素。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，而且对于解决中枢神经系统沟通障碍的行为策略的发展也是至关重要的。 该提议着重于内侧上橄榄（MSO），这是脑干中的主要上升听觉途径，它传达了有关低频声音的时间结构和位置的信息。 MSO的投射神经元检测到声音到达的次毫秒差距到两只耳朵，并将这些线索传输到更高的听觉中心。在每个MSO神经元内，是否要信号的决定取决于树突中突触输入的整合，即接收大多数突触输入的狭窄，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中记录电活动的技术困难，它们的功能仍未被调查。 本研究将将树突状贴剂记录与脑切片中的钙成像相结合，以检查中央听觉神经元中的第一次树突整合。首先，实验将检验以下假设：电压门控通道塑造了MSO主神经元对子阈值突触活动的反应以及动作电位的启动和传播。其次，我们将探讨以下假设：在发育过程中，突触连接与MSO神经元的强度是塑性的，并且受神经元中固有离子通道的调节。最后，实验将提出以下假设：细胞内钙的流入是将固有电压和韧带的活性与随后的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开发过程中行为上适当连接的形成的基础，并且可能代表了中央听觉系统低水平的听觉学习形式。