Acute stress effects on cognition and synaptic plasticity

急性应激对认知和突触可塑性的影响

• 批准号: 355868-2008
• 负责人: Howland, John
• 金额: $ 1.82万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=497183
• 关键词: Acute; stress; effects; cognition; synaptic

My Discovery Grant Program is designed to elucidate the mechanisms underlying the effects of experience on neurophysiology and cognitive functions such as memory. Neurophysiological processes and memory are strongly influenced by a variety of experiences, such as acute stress. However, definitive links between the effects of experience on particular neurophysiological processes, such as patterns of synaptic plasticity, and memory are lacking. The specific experiments in the present proposal are designed to determine the effects of one particular experience, that of acute stress, on memory retrieval in rodents. We have recently developed sensitive behavioral tests that may be used to reliably assess two types of memory, recognition and temporal order memory, in rodents. When these tests are conducted with different stimuli (spatial information or objects), normal memory performance depends on well understood, dissociable circuits involving a number of brain areas including the hippocampus, perirhinal cortex, and medial prefrontal cortex. In an initial series of experiments, the effects of acute stress on memory retrieval in these tests will be examined. We believe that acute stress will disrupt normal memory retrieval on these tests thereby providing novel information regarding the specific types of memory and neural substrates influenced by acute stress. In separate electrophysiological experiments, the effects of acute stress on synaptic plasticity in the neural circuits important for performance of these tests will be characterized. Given the results of previous experiments, acute stress is predicted to enable the induction of a cellular model of synaptic plasticity known as long-term depression in the hippocampus, perirhinal cortex, and medial prefrontal cortex. Finally, the effects of a number of highly specific inhibitors known to inhibit long-term depression in other preparations will be used to block the electrophysiological and behavioral effects of acute stress. An integration of the fundamental behavioral and electrophysiological effects of acute stress on learning and memory will allow theories regarding the neural mechanisms mediating cognition in both normal and challenging circumstances to be developed.

我的发现资助计划旨在阐明经验对神经生理学和认知功能（如记忆）影响的潜在机制。神经生理过程和记忆受到各种经历的强烈影响，例如急性应激。然而，经验对特定神经生理过程（如突触可塑性模式）的影响与记忆之间缺乏明确的联系。本研究的具体实验旨在确定一种特殊的经历，即急性应激对啮齿动物记忆恢复的影响。我们最近开发了敏感的行为测试，可以用来可靠地评估啮齿动物的两种记忆，识别和时间顺序记忆。当这些测试用不同的刺激（空间信息或物体）进行时，正常的记忆表现取决于被充分理解的、可分离的回路，涉及许多大脑区域，包括海马体、鼻周皮层和内侧前额皮质。在最初的一系列实验中，我们将考察急性应激对这些测试中记忆提取的影响。我们认为急性应激会破坏这些测试中的正常记忆检索，从而提供关于急性应激影响的特定类型的记忆和神经基质的新信息。在单独的电生理实验中，急性应激对神经回路突触可塑性的影响对这些测试的表现很重要。根据之前的实验结果，我们预测急性应激能够诱导海马、鼻周皮层和内侧前额叶皮层的突触可塑性细胞模型，即长期抑制。最后，在其他制剂中已知的一些高度特异性抑制长期抑郁的抑制剂的作用将被用于阻断急性应激的电生理和行为效应。急性应激对学习和记忆的基本行为和电生理影响的整合将使有关正常和挑战性环境下调节认知的神经机制的理论得以发展。