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.

声音的时变特征是人类和其他哺乳动物不仅用于理解语音和其他通信信号，而且还用于定位声音的关键线索。这项研究的长期目标是了解形成这些功能背后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觉的神经生物学基础至关重要，而且对于解决中枢神经系统通信障碍的行为策略的发展也至关重要。 该建议的重点是内侧上级橄榄（MSO），脑干中的主要上行听觉通路，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双耳时的亚毫秒时间差异，并将这些线索传递到更高的听觉中心。在每个MSO神经元内，是否发出信号的决定取决于树突中突触输入的整合，树突是接收大部分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记录电活动的技术困难，它们的功能仍然未被研究。 本研究将联合收割机技术与脑片钙离子成像技术相结合，首次研究中枢听觉神经元的树突整合。首先，实验将测试的假设，电压门控通道形状的MSO主神经元的反应，亚阈值突触活动以及动作电位的启动和传播。其次，我们将探讨的假设，突触连接到MSO神经元的强度是可塑性的，在发育过程中，并在神经元的内在离子通道调节。最后，实验将追求的假设，即细胞内钙离子内流的细胞机制，连接活动的内在电压和ligandgated通道与随后的变化突触强度。这些突触强度的变化可能是发育过程中行为适当连接形成的基础，也可能是中枢听觉系统低水平听觉学习的一种形式。