EAGER: Identifying network dynamics promoting memory consolidation during sleep
EAGER:识别网络动态促进睡眠期间的记忆巩固
基本信息
- 批准号:1749430
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
While the exact physiological function of sleep remains unknown, there is mounting evidence that it plays an important role in the consolidation of long-term memories. In particular, it appears that sleep promotes the consolidation of declarative memories that require a functionally intact hippocampus, including memories of place. In rodents, place-dependent fear memory is promoted by sleep and disrupted by sleep deprivation. Sleep deprivation also disrupts a number biochemical and neurophysiological processes that are thought to be involved in memory consolidation. These studies have led many to suggest that sleep promotes long-term memory consolidation by modulating neural network dynamics and synaptic plasticity within the hippocampus. In experimental studies, the co-PIs have recently identified changes in hippocampal neural network dynamics during sleep that are induced by place-dependent fear learning. In computational modeling studies, the co-PIs have shown that acetylcholine, a modulatory chemical whose levels vary across sleep states, can change neural network dynamics in a similar way. The proposed projects take a multidisciplinary, multi-scale approach to bridge the gap between experimental and computational results, to identify how effects of acetylcholine on neurons lead to changes in neural network dynamics to promote learning, ultimately leading to learning and memory behavior. While the focus is on fear learning and memory consolidation, the fundamental knowledge of learning-related and sleep-related brain network dynamics gained by the proposed experiments and computations will provide valuable insights into mechanisms for all types of learning.At present, it is unclear how sleep-related changes in hippocampal network dynamics might promote contextual fear memory consolidation. The team's recent experimental studies have shown that contextual fear conditioning produces long-lasting, sleep-dependent increases in the stability of hippocampal network functional connectivity patterns. These results, coupled with the team's recent computational studies describing a role for acetylcholine in network-wide activity and synaptic plasticity patterning, have led to the hypothesis that sleep promotes memory consolidation, at least in part, by dynamically shifting patterns in hippocampal neural network activity during naturally-occurring rapid eye movement and slow wave sleep brain states. Sleep-dependent acetylcholine has a primary role in driving these shifts in network activity through its effects on cellular excitability properties. The proposed projects use behavioral, physiological, and computational approaches to tackle the missing links that will show the hypothesized network mechanisms occur in brain hippocampal networks and participate in fear learning and memory. Hippocampal acetylcholine levels will be manipulated across wake and sleep states while recording multi-unit activity in hippocampus to quantify changes in spike timing dynamics in the context of fear and subsequent sleep or sleep deprivation. The team has developed a suite of quantitative measures to identify learning-related changes in network dynamics. In addition, acetylcholine-induced changes in cellular membrane properties that affect network dynamics will be measured in hippocampal pyramidal cell and inhibitory interneuron populations. The results will be used to inform details of biophysical neural network models to identify specific dynamical mechanisms by which acetylcholine-mediated changes in network activity dynamics promote network stability, structural changes and synaptic reorganization associated with learning and consolidation.
虽然睡眠的确切生理功能尚不清楚,但越来越多的证据表明,它在巩固长期记忆方面发挥着重要作用。特别是,睡眠似乎促进了需要功能完整的海马体的陈述性记忆的巩固,包括对地点的记忆。在啮齿动物中,位置依赖的恐惧记忆被睡眠促进,并被睡眠剥夺所扰乱。睡眠不足还会扰乱一些被认为与记忆巩固有关的生化和神经生理过程。这些研究导致许多人认为,睡眠通过调节神经网络动力学和海马体内突触的可塑性来促进长期记忆巩固。在实验研究中,联合PI最近发现了位置依赖恐惧学习导致的睡眠期间海马神经网络动力学的变化。在计算模型研究中,联合PI表明,乙酰胆碱可以以类似的方式改变神经网络的动力学。乙酰胆碱是一种调节性化学物质,其水平在不同的睡眠状态下会有所不同。拟议的项目采用多学科、多尺度的方法来弥合实验和计算结果之间的差距,以确定乙酰胆碱对神经元的影响如何导致神经网络动力学的变化以促进学习,最终导致学习和记忆行为。虽然重点放在恐惧学习和记忆巩固上,但通过拟议的实验和计算获得的与学习相关和睡眠相关的脑网络动力学基础知识将为所有类型的学习机制提供有价值的见解。目前,尚不清楚与睡眠相关的海马网动态变化如何促进背景恐惧记忆的巩固。该团队最近的实验研究表明,情景恐惧条件作用在海马体网络功能连接模式的稳定性方面产生长期的、依赖睡眠的增加。这些结果,再加上该团队最近的计算研究,描述了乙酰胆碱在整个网络活动和突触可塑性模式中的作用,导致了一种假设,即睡眠至少在一定程度上通过在自然发生的快速眼动和慢波睡眠大脑状态下动态改变海马神经网络活动的模式来促进记忆巩固。睡眠依赖的乙酰胆碱通过对细胞兴奋性属性的影响,在推动网络活动的这些转变中发挥了主要作用。拟议的项目使用行为、生理和计算方法来解决缺失的环节,这些环节将显示假设的网络机制发生在大脑海马网络中,并参与恐惧的学习和记忆。海马乙酰胆碱水平将在清醒和睡眠状态下被操纵,同时记录海马体中的多个单位的活动,以量化恐惧和随后的睡眠或睡眠剥夺背景下尖峰定时动态的变化。该团队开发了一套量化措施,以确定网络动态中与学习相关的变化。此外,将在海马锥体细胞和抑制性中间神经元群体中测量乙酰胆碱引起的影响网络动力学的细胞膜属性的变化。这些结果将被用来为生物物理神经网络模型的细节提供信息,以确定特定的动力学机制,通过这些机制,乙酰胆碱介导的网络活动动态变化促进网络稳定性、结构变化以及与学习和巩固相关的突触重组。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Acetylcholine Mediates Dynamic Switching Between Information Coding Schemes in Neuronal Networks
乙酰胆碱介导神经网络中信息编码方案之间的动态切换
- DOI:10.3389/fnsys.2019.00064
- 发表时间:2019
- 期刊:
- 影响因子:3
- 作者:Roach, James P.;Eniwaye, Bolaji;Booth, Victoria;Sander, Leonard M.;Zochowski, Michal R.
- 通讯作者:Zochowski, Michal R.
Theta-gamma coupling emerges from spatially heterogeneous cholinergic neuromodulation.
- DOI:10.1371/journal.pcbi.1009235
- 发表时间:2021-07
- 期刊:
- 影响因子:4.3
- 作者:Yang Y;Gritton H;Sarter M;Aton SJ;Booth V;Zochowski M
- 通讯作者:Zochowski M
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Victoria Booth其他文献
Network effects of frequency dependent phase response curves
- DOI:
10.1186/1471-2202-11-s1-p40 - 发表时间:
2010-07-20 - 期刊:
- 影响因子:2.300
- 作者:
Chris Fink;Victoria Booth;Michal Zochowski - 通讯作者:
Michal Zochowski
Accuracy Versus Predominance: Reassessing the Validity of the Quasi-Steady-State Approximation
- DOI:
10.1007/s11538-025-01451-z - 发表时间:
2025-05-16 - 期刊:
- 影响因子:2.200
- 作者:
Kashvi Srivastava;Justin Eilertsen;Victoria Booth;Santiago Schnell - 通讯作者:
Santiago Schnell
Interaction of membrane dynamics with network structure and its effects on spatio-temporal network patterning
- DOI:
10.1186/1471-2202-9-s1-p147 - 发表时间:
2008-07-11 - 期刊:
- 影响因子:2.300
- 作者:
Andrew Bogaard;Michal Zochowski;Victoria Booth - 通讯作者:
Victoria Booth
Acetylcholine and synaptic homeostasis
- DOI:
10.1186/1471-2202-13-s1-o6 - 发表时间:
2012-07-16 - 期刊:
- 影响因子:2.300
- 作者:
Christian G Fink;Victoria Booth;Michal Zochowski - 通讯作者:
Michal Zochowski
Network heterogeneity and seizure generation
- DOI:
10.1186/1471-2202-16-s1-p302 - 发表时间:
2015-12-18 - 期刊:
- 影响因子:2.300
- 作者:
Sima Mofakham;Christian G Fink;Victoria Booth;Michal R Zochowski - 通讯作者:
Michal R Zochowski
Victoria Booth的其他文献
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{{ truncateString('Victoria Booth', 18)}}的其他基金
Collaborative Research: Nonsmooth Maps, Coupled Oscillators and Seasonal Variation of Sleep and Circadian Rhythms
合作研究:非平滑图、耦合振荡器以及睡眠和昼夜节律的季节变化
- 批准号:
1853506 - 财政年份:2019
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
Collaborative Research: Multiscale Modeling of the Physiological Interactions Between Sleep/Wake and Circadian Systems
合作研究:睡眠/觉醒与昼夜节律系统之间的生理相互作用的多尺度建模
- 批准号:
1412119 - 财政年份:2014
- 资助金额:
$ 30万 - 项目类别:
Continuing Grant
ADVANCE Fellows Award: Theta phases of hippocampal place cell firing in REM sleep and waking
ADVANCE 研究员奖:快速眼动睡眠和清醒时海马位置细胞放电的 Theta 相
- 批准号:
0340687 - 财政年份:2004
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
A Dendritic Origin of Bistability of Motoneuron Firing Patterns
运动神经元放电模式双稳定性的树突起源
- 批准号:
9722946 - 财政年份:1997
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
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