Time-Dependent Effects of Stress on Learning: Physiological and Genetic Associations

压力对学习的时间依赖性影响：生理和遗传关联

基本信息

  • 批准号：
    8851344
  • 负责人：
    Phillip Zoladz
  • 金额：
    $ 42.38万
  • 依托单位：
    OHIO NORTHERN UNIVERSITY
  • 依托单位国家：
    美国
  • 项目类别：
  • 财政年份：
    2015
  • 资助国家：
    美国
  • 起止时间：
    2015-05-01 至 2018-08-20
  • 项目状态：
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Stress-induced alterations of learning and memory have important implications for understanding the development of post-traumatic stress disorder (PTSD). Researchers have speculated that traumatic stress may promote the onset of PTSD as a result of pre-existing genetic factors and peri-traumatic physiological responses influencing learning and, thus, traumatic memory formation. Indeed, investigators have established a clear association between certain genetic polymorphisms, emotional memory and the onset of PTSD. However, systematic examination, in clinical samples, of susceptibility factors that could promote traumatic memory formation is problematic, making basic models of stress-memory interactions a necessity. It is still unclear as to what factors are most important for dictating te types of effects stress exerts on learning and memory and when the effects promote the formation of intrusive, debilitating memories. One leading theory regarding stress effects on learning is the temporal dynamics model of emotional memory processing. According to this theory, stress exerts biphasic effects on learning as a result of amygdala-induced modulation of hippocampal synaptic plasticity. Specifically, stress rapidly activates the amygdala, which enhances hippocampal plasticity and promotes the formation of powerful emotional memories; however, as stress continues, the hippocampus enters a refractory state during which hippocampal plasticity, and thus learning, is impaired. We have preliminary data supporting these predictions for declarative learning in humans; however, the mechanisms underlying these effects are still unclear, and an examination of how stressor timing influences other forms of learning that may relate better to traumatic memory formation, such as fear conditioning and extinction, has not yet been conducted. Moreover, sex differences are common in the stress-memory literature, yet little work has examined the role of sex in time-dependent effects of stress on learning. Thus, in Aim 1, we will examine how the timing of pre-learning stress interacts with individual characteristics (e.g., autonomic and endocrine stress responses, sex) to influence declarative learning and fear conditioning. Since there has been little work examining how genetic polymorphisms associated with emotional memory and stress increases one's risk for traumatic memory formation, this will be the focus of Aim 2. We will genotype participants from the studies in Aim 1 for single nucleotide polymorphisms (SNPs) that have been associated with the physiological stress response, emotional memory and/or risk for PTSD and examine whether such SNPs are associated with participants' physiological response to/recovery from stress exposure, as well as any observed stress-induced alterations of learning and memory. These studies will contribute important knowledge about when stress enhances versus impairs learning and memory and the physiological mechanisms underlying such effects. The findings may also lend insight into risk factors for traumatic memory formation and potentially facilitate the development of more targeted treatment options for PTSD in the future.
 描述(由申请人提供)：压力诱导的学习和记忆改变对于理解创伤后应激障碍(PTSD)的发展具有重要意义。研究人员推测，创伤应激可能会促进创伤后应激障碍的发生，这是由于先前存在的遗传因素和创伤周围的生理反应影响了学习，从而形成了创伤记忆。事实上，研究人员已经在某些基因多态、情绪记忆和创伤后应激障碍的发病之间建立了明确的联系。然而，在临床样本中对可能促进创伤性记忆形成的易感因素进行系统检查是有问题的，这使得压力-记忆相互作用的基本模型成为必要。目前还不清楚哪些因素是决定压力对学习和记忆施加的影响类型的最重要因素，以及这些影响何时促进了侵入性、衰弱记忆的形成。关于压力对学习的影响的一个主要理论是情绪记忆处理的时间动力学模型。根据这一理论，由于杏仁核诱导的海马突触可塑性的调节，应激对学习产生双相影响。具体地说，压力会迅速激活杏仁核，增强海马体的可塑性，促进强大的情感记忆的形成；然而，随着应激的持续，海马体进入难治状态，在此期间，海马体的可塑性和学习能力受到损害。我们有初步数据支持人类陈述性学习的这些预测；然而，这些效应背后的机制仍然不清楚，而且还没有研究应激源时机如何影响其他形式的学习，这些形式可能与创伤性记忆的形成更好地相关，如恐惧条件反射和消退。此外，性别差异在压力记忆文献中很常见，但很少有工作研究性别在压力对学习的时间依赖效应中所起的作用。因此，在目标1中，我们将研究学习前应激的时机如何与个体特征(如自主和内分泌应激反应、性别)相互作用，以影响陈述性学习和恐惧条件反射。由于很少有人研究与情绪记忆和压力相关的基因多态如何增加创伤性记忆形成的风险，这将是目标2的重点。我们将对目标1中研究的参与者进行单核苷酸多态(SNPs)的基因分型，这些SNP与生理应激反应、情绪记忆和/或创伤后应激障碍的风险相关，并检查这些SNP是否与参与者对应激的生理反应/从应激中恢复，以及任何观察到的应激诱导的学习和记忆改变有关。这些研究将对压力何时增强或损害学习和记忆以及这种影响背后的生理机制提供重要的知识。这些发现还可能有助于深入了解创伤记忆形成的风险因素，并有可能促进未来为创伤后应激障碍开发更有针对性的治疗方案。

项目成果

期刊论文数量（5）
专著数量（0）
科研奖励数量（0）
会议论文数量（0）
专利数量（0）
ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory.
ADRA2B 缺失变异会影响学前压力对长期记忆的时间依赖性影响。
  • DOI：
    10.1016/j.nlm.2017.02.014
  • 发表时间：
    2017
  • 期刊：
    Neurobiology of learning and memory
  • 影响因子：
    2.7
  • 作者：
    Zoladz,PhillipR;Dailey,AlisonM;Nagle,HannahE;Fiely,MirandaK;Mosley,BrianneE;Brown,CallieM;Duffy,TessaJ;Scharf,AmandaR;Earley,McKennaB;Rorabaugh,BoydR
  • 通讯作者：
    Rorabaugh,BoydR
FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.
FKBP5 多态性影响学习前压力引起的学习和记忆改变。
  • DOI：
    10.1111/ejn.13514
  • 发表时间：
    2017
  • 期刊：
    The European journal of neuroscience
  • 影响因子：
    0
  • 作者：
    Zoladz,PhillipR;Dailey,AlisonM;Nagle,HannahE;Fiely,MirandaK;Mosley,BrianneE;Brown,CallieM;Duffy,TessaJ;Scharf,AmandaR;Earley,McKennaB;Rorabaugh,BoydR
  • 通讯作者：
    Rorabaugh,BoydR
Interactive influence of sex, stressor timing, and the BclI glucocorticoid receptor polymorphism on stress-induced alterations of long-term memory.
性别、压力源时间和 BclI 糖皮质激素受体多态性对压力引起的长期记忆改变的交互影响。
  • DOI：
    10.1016/j.bandc.2018.05.012
  • 发表时间：
    2019
  • 期刊：
    Brain and cognition
  • 影响因子：
    2.5
  • 作者：
    Zoladz,PhillipR;Duffy,TessaJ;Mosley,BrianneE;Fiely,MirandaK;Nagle,HannahE;Scharf,AmandaR;Brown,CallieM;Earley,McKennaB;Rorabaugh,BoydR;Dailey,AlisonM
  • 通讯作者：
    Dailey,AlisonM
Immediate pre-learning stress enhances baseline startle response and fear acquisition in a fear-potentiated startle paradigm.
在恐惧增强的惊吓范式中，立即的学前压力增强了基线惊吓反应和恐惧习得。
  • DOI：
    10.1016/j.bbr.2019.111980
  • 发表时间：
    2019
  • 期刊：
    Behavioural brain research
  • 影响因子：
    2.7
  • 作者：
    Riggenbach,MackenzieR;Weiser,JordanN;Mosley,BrianneE;Hipskind,JenniferJ;Wireman,LeightonE;Hess,KelseyL;Duffy,TessaJ;Handel,JulieK;Kaschalk,MacKenzieG;Reneau,KassidyE;Rorabaugh,BoydR;Norrholm,SethD;Jovanovic,Tanja;Zola
  • 通讯作者：
    Zola
Blunted cortisol response to acute pre-learning stress prevents misinformation effect in a forced confabulation paradigm.
对急性学习前压力的皮质醇反应迟钝可以防止强制虚构范式中的错误信息效应。
  • DOI：
    10.1016/j.yhbeh.2017.04.003
  • 发表时间：
    2017
  • 期刊：
    Hormones and behavior
  • 影响因子：
    3.5
  • 作者：
    Zoladz,PhillipR;Cadle,ChelseaE;Dailey,AlisonM;Fiely,MirandaK;Peters,DavidM;Nagle,HannahE;Mosley,BrianneE;Scharf,AmandaR;Brown,CallieM;Duffy,TessaJ;Earley,McKennaB;Rorabaugh,BoydR;Payment,KristieE
  • 通讯作者：
    Payment,KristieE
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Phillip Zoladz其他文献

Phillip Zoladz的其他文献

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