Impact of network oscillations on dendritic computation in hippocampal pyramidal neurons

网络振荡对海马锥体神经元树突计算的影响

基本信息

批准号：
9761836
负责人：
Sebastian Victor Rolotti
金额：
$ 4.5万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9761836
关键词：
Action Potentials Address Alzheimer&apos s Disease Anatomy Animals Apical Area Attention Behavior Behavioral Calcium Cell physiology Cells Chemosensitization Chronic Computer software Conceptions Coupled Coupling Data Dendrites Development Distal Electrophysiology (science)Environment Epilepsy Event Generations Goals Grant Head Hippocampal Formation Hippocampus (Brain)Image Impairment Individual Knowledge Label Learning Link Location Maintenance Memory Methods Monitor Mus Neurons Organism Output Pathology Physiological Play Population Prevalence Process Property Pyramidal Cells Research Resolution Rewards Rodent Role Sensory Shapes Signal Transduction Site Synapses Synaptic plasticity Testing Training Update Work awake extracellular hippocampal pyramidal neuron hippocampal subregions in vivo learned behavior memory consolidation nervous system disorder novel optical imaging recruit regenerative spatial memory submicron two-photon way finding

项目摘要

Project Summary/Abstract Perhaps the fundamental property of a neuron is its ability to integrate and transform diverse inputs into a singular train of action potential output. This capacity is what enables circuits of neurons to combine environmental features and internal states to drive an organism’s behavior. Dendrites, the primary sites of synaptic input integration, are capable of generating local regenerative events known as dendritic spikes. Recent in vivo work points to the importance of dendritic spiking to behavior and has demonstrated a role for these events in synaptic plasticity, feature selectivity, and learning in cortical and non-cortical areas. In particular, there has been significant recent progress connecting the dynamics of dendritic spiking in CA1 pyramidal cells (CA1 PCs) during active exploration to the formation and maintenance of CA1 PC spatial tuning. It has therefore become clear that an understanding of in vivo dendritic dynamics in CA1 PCs is critical for elucidating the computational roles of CA1 PCs in hippocampal spatial memory function. In parallel, the role of CA1 network activity in spatial memory function during immobility is also recently being actively explored. Sharp-wave ripples (SWRs), the predominant network event during awake immobility, are thought to enable synaptic potentiation in CA1 PCs previously co-active during exploration. Through this mechanism, SWRs have been implicated in memory consolidation and spatial learning. A major knowledge gap remains concerning how these population-level network states alter dendritic dynamics in CA1 PCs. The goal of the proposed research is to connect CA1 network dynamics to the dendritic dynamics determining cellular participation in spatial navigation and memory tasks. This proposal implements several recent advances in optical imaging and extracellular electrophysiology methods in the mouse, allowing us to longitudinally monitor the activity of the dendrites and cell bodies of hippocampal neurons with submicron resolution while simultaneously recording network oscillations over many days as the animal engages in various navigation and learning behaviors. Using these methods, I will address the central hypothesis of this application, that SWRs persistently alter the mode of dendritic integration of recruited CA1 PCs and that these mode changes will in turn determine the cell’s spatial memory function. Aim 1 will test whether the activity of dendrites active during SWRs are stabilized, and if this has an impact on the day to day stability of CA1 PC spatial tuning. Aim 2 will examine how dendritic activity during SWRs shapes the way CA1 PC spatial tuning is altered by rewards in a spatial learning task. In summary, this work will use chronic extracellular electrophysiology and simultaneous multiplane two-photon imaging of CA1 PC dendritic and somatic activity during learning in the awake rodent to further our understanding of the interplay of network and dendritic dynamics on hippocampal spatial memory function.

项目概要/摘要也许神经元的基本属性是它能够将不同的输入整合并转化为这种能力使得神经元电路能够组合起来。驱动生物体行为的环境特征和内部状态。树突是生物体的主要场所。突触输入整合能够产生称为树突尖峰的局部再生事件。最近的体内工作指出了树突尖峰对行为的重要性，并证明了其作用这些事件涉及突触可塑性、特征选择性以及皮质和非皮质区域的学习。特别是，最近在 CA1 树突尖峰动力学方面取得了重大进展锥体细胞（CA1 PC）在积极探索CA1 PC空间的形成和维持过程中因此，很明显，了解 CA1 PC 的体内树突动力学至关重要。阐明 CA1 PC 在海马空间记忆功能中的计算作用。与此同时，CA1 网络活动在不动期间空间记忆功能中的作用最近也得到了研究。锐波波纹（SWR）是清醒不动期间的主要网络事件，被认为可以在探索过程中先前共同活跃的 CA1 PC 中实现突触增强。 SWR 与记忆巩固和空间学习有关。关于这些群体水平的网络状态如何改变 CA1 PC 中的树突动态仍然存在差距。本研究的目标是将 CA1 网络动力学与树突动力学联系起来确定细胞参与空间导航和记忆任务该提案实施了几个。小鼠光学成像和细胞外电生理学方法的最新进展使我们能够用亚微米纵向监测海马神经元树突和细胞体的活动分辨率，同时记录动物参与多天的网络振荡使用这些方法，我将解决这个的中心假设。应用程序中，SWR 持续改变招募的 CA1 PC 的树突整合模式，并且这些模式的变化将反过来决定细胞的空间记忆功能是否活跃。 SWR 期间活跃的树突已稳定，这是否对 CA1 PC 的日常稳定性有影响目标 2 将研究 SWR 期间的树突活动如何影响 CA1 PC 空间调谐的方式。空间学习任务中的奖励会改变总之，这项工作将使用慢性细胞外。 CA1 PC 树突和体细胞活动的电生理学和同时多平面双光子成像在清醒啮齿动物的学习过程中，进一步了解网络和树突的相互作用海马空间记忆功能的动态变化。