Acute stress effects on cognition and synaptic plasticity

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。 在本建议中的具体实验旨在确定一个特定的经验，即急性应激，对啮齿动物的记忆提取的影响。 我们最近开发了敏感的行为测试，可用于可靠地评估两种类型的记忆，识别和时间顺序记忆，在啮齿动物。 当这些测试是用不同的刺激（空间信息或物体）进行的时候，正常的记忆表现取决于我们已经很好理解的、可分离的回路，这些回路涉及许多大脑区域，包括海马体、嗅周皮层和内侧前额叶皮层。 在最初的一系列实验中，将检查急性应激对这些测试中记忆提取的影响。 我们相信，急性应激会破坏正常的记忆检索这些测试，从而提供新的信息，关于特定类型的记忆和神经基板的影响，急性应激。 在单独的电生理学实验中，急性应激对神经回路中突触可塑性的影响将被表征，这些神经回路对这些测试的性能很重要。 鉴于先前的实验结果，急性应激被预测能够诱导海马体、嗅周皮层和内侧前额叶皮层中的突触可塑性的细胞模型，称为长期抑郁。 最后，一些高度特异性的抑制剂的影响，已知抑制长期抑郁症的其他制剂将被用来阻止急性应激的电生理和行为的影响。 急性应激对学习和记忆的基本行为和电生理效应的整合将允许关于在正常和具有挑战性的情况下介导认知的神经机制的理论被开发。

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.