Neuroendocrine modulation of LTP durability

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。对一段经历的激素反应可以衡量这段经历被记住的程度和时间。 肾上腺素（肾上腺素）就是这样一种激素调节记忆力和持久性。 PI最近的研究结果，使用称为长时程增强（LTP）的记忆电生理模型，表明肾上腺素还调节大鼠记忆相关脑区中称为突触的神经元之间连接的强度和持久性。 具体来说，注射肾上腺素将LTP的持续时间从没有肾上腺素时的几分钟延长到几天。 该建议检查神经网站和分子机制的重要性，这种转换的短期到长期持续的LTP的肾上腺素。目标1将测试两个大脑区域的活动，海马体和杏仁核，这两个区域在记忆形成中很重要。 肾上腺素可能通过杏仁核中的特异性受体间接调节LTP强度和持久性，并通过海马中的受体直接影响LTP强度，海马是突触强度变化的部位。 目标2将检查参与转换为持久突触强度的分子事件，重点是一种蛋白质CREB的激活，该蛋白质调节许多基因的表达。 预测是CREB活性的增加将对应于突触强度的增加的耐久性。这些研究的结果将有助于深入了解压力激素，强烈情绪的一个组成部分，如何导致强烈的记忆。 这些实验的科学影响可能是广泛的，其发现将促进记忆机制，神经内分泌学和神经生理学领域的知识，将基本发现扩展到学习，生殖和动物行为领域。 该项目将为本科生和高中生提供广泛，独特的研究经验，由PI和学生使用书面，技术和主观报告的组合评估进展。 再加上PI开展的各种推广计划，这些机会将影响广泛而多样化的未来科学家群体。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Hormonal responses to an experience can gate how well and for how long the experience is remembered. Epinephrine (adrenaline) is one such hormonal regulator of memory strength and durability. Recent findings by the PI, using an electrophysiological model of memory called long-term potentiation (LTP), demonstrate that epinephrine also modulates the strength and durability of connections between neurons known as synapses in brain areas involved in memory in rats. Specifically, an injection of epinephrine extends LTP durability from minutes, seen without epinephrine, to days. This proposal examines the neural sites and molecular mechanisms important to this conversion of short- to long-lasting LTP by epinephrine. Aim 1 will test actions at two brain regions, the hippocampus and amygdala, important in memory formation. Epinephrine likely modulates LTP strength and durability indirectly via specific receptors in the amygdala and directly influences LTP strength through receptors in the hippocampus, the site of change in synaptic strength. Aim 2 will examine molecular events involved in the conversion to long lasting synaptic strength, focusing on the activation of one protein, CREB, that regulates the expression of many genes. Predictions are that increases in CREB activity will correspond to increased durability of synaptic strength. Results from these studies will lend insight into how stress hormones, a component of strong emotions, lead to strong memories. The scientific impact of these experiments is potentially broad with findings that will advance knowledge in fields of mechanisms of memory, neuroendocrinology, and neurophysiology, extending basic findings to fields of learning, reproduction, and animal behavior. This project will provide extensive, unique research experiences for undergraduate and high-school students, with progress assessed by PIs and students using portfolios of written, technical, and subjective reports. Together with the varied outreach programs the PIs conduct, these opportunities will impact a wide and diverse group of prospective scientists.