Neuroendocrine modulation of LTP durability

LTP 持久性的神经内分泌调节

• 批准号: 0843175
• 负责人: Donna Korol
• 金额: $ 56.85万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0843175&HistoricalAwards=false
• 关键词: Neuroendocrine; modulation; LTP; durability

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.

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。荷尔蒙对一种经历的反应可以决定这种经历被记住的程度和时间。肾上腺素（肾上腺素）就是一种调节记忆强度和持久性的激素。PI最近的研究发现，使用一种叫做长期增强（LTP）的记忆电生理模型，表明肾上腺素还能调节老鼠大脑中与记忆有关的神经元（突触）之间连接的强度和持久性。具体来说，注射肾上腺素可以延长LTP的持续时间，从没有肾上腺素时的几分钟延长到几天。本研究探讨了肾上腺素将短期LTP转化为长期LTP的重要神经位点和分子机制。目的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定受体间接调节LTP的强度和持久性，并通过海马中的受体（突触强度变化的部位）直接影响LTP的强度。目的2将研究与转化为持久突触强度有关的分子事件，重点关注一种调节许多基因表达的蛋白质CREB的激活。预测CREB活动的增加将与突触强度的持久性增加相对应。这些研究的结果将有助于深入了解压力激素（强烈情绪的组成部分）是如何导致强烈记忆的。这些实验的科学影响可能是广泛的，其发现将推进记忆机制、神经内分泌学和神经生理学领域的知识，将基础发现扩展到学习、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而独特的研究经验，由pi和学生使用书面、技术和主观报告组合评估进展。加上pi开展的各种外展项目，这些机会将影响到广泛而多样化的未来科学家群体。