Amygdala neural circuits in alcohol intake

项目摘要 这种多样性补充申请将支持神经科学研究生，马蒂尔德卡斯特罗，在2年 与支持研究的母基金R 01-AA 027213相关但不多余的培训计划 进入杏仁核和大脑皮层回路在大鼠寻求酒精自我管理模型。女士 卡斯特罗准备进行一段密集的研究，以获得酒精神经生物学研究的专业知识， 动物模型，并在研究的科学和专业方面接受高质量的指导。的 这次强化培训的目的是让卡斯特罗女士为培训的下一步做好准备;具体来说， 在补充期间获得的将1）形成2-4个第一作者出版物的基础; 2）将 为F31应用程序提供初步数据，从而推动她在她的独立性 研究生涯。这项投资将为她实现研究职业目标提供宝贵的推动力， 这将使NIH在生物医学研究中实现多样性的目标得以继续推进。在我们的世界里， 了解血清素如何影响CeA的酒精相关功能，卡斯特罗女士将确定 CeA中5 HT 2A受体在酒精寻求/服用中的作用，使用电生理学，药理学， 光遗传学在目标1中，她将确定5 HT 2a受体对CeA神经活动的影响;在目标2中， 她将测试微量输注5 HT 2a激动剂或拮抗剂是否会改变酒精寻求和/或服用; 3，她将使用光遗传学来逆转5 HT 2a操纵后寻求酒精的减少， 链接.这些研究与父母补助金的目标一致，特别是Aim 1，它定义了神经系统疾病。 在乙醇自我给药期间，CeA、PSV和PVT的活性模式。在Aim 1中，卡斯特罗女士将 利用体内电生理学研究CeA神经活动，但她专注于一个新的角度，即 血清素和5 HT 2a受体的作用。此外，在父母补助金的目标3中，我们使用光遗传学来 检查酒精自我管理的CeA神经通路的操纵。与Aim 3一样，卡斯特罗女士将 我也使用光遗传学来研究，但在这里，她将测试一个新的假设，即激活CeA在一个线索， 将逆转5 HT 2a受体激活的急性效应。除了注重行政首长理事会之外， 补充研究与父母补助金是一致的，但不是重复的，因为他们没有使用共同的补助金。 行为模型，DT 3寻找-接受程序，允许在寻找过程中隔离神经过程 在服用过程中。在卡斯特罗女士的案例中，这将有助于她了解神经行为机制， 5 HT 2a受体调节。因此，这些研究扩展了父母补助金的总体目标，以更好地了解 酒精作用中的CeA机制。卡斯特罗女士的研究将补充家长的总体目标 通过提供一个独立的集合来了解CeA在酒精自我管理中的作用 的发现。在进行研究的同时，卡斯特罗女士和我将共同努力实现她的目标， 包括口头报告、手稿准备和NRSA F31提交强化指导。

PROJECT SUMMARY This diversity supplement application will support neuroscience graduate student, Matilde Castro, in a 2yr training program relevant to, but not redundant with, parent grant R01-AA027213, which supports investigation into amygdala and insula cortex circuitry in a rat seeking-taking model of alcohol self-administration. Ms. Castro is ready for an intensive period of research to gain expertise in neurobiological studies of alcohol in animal models and to receive high-quality mentoring in scientific and professional aspects of research. The purpose of this intensive training is to prepare Ms. Castro for next steps in her training; specifically, data she obtains during the period of the supplement will 1) form the basis of 2-4 1st-author publications; and 2) will provide preliminary data for an F31 application, thus propelling her towards reaching independence in her research career. This investment will give her a valuable boost towards meeting her research career goals and will enable continued advancement of NIH goals for diversity in biomedical research. There is a gap in our understanding of how serotonin impacts the alcohol-related functions of the CeA, Ms. Castro will determine the role of the 5HT2A receptor in the CeA on alcohol seeking/taking, using electrophysiology, pharmacology, and optogenetics. In Aim 1 she will determine the impact of the 5HT2a receptor on CeA neural activity; in Aim 2 she will test whether microinfusion of 5HT2a agonists or antagonists alter alcohol seeking and/or taking; in Aim 3, she will use optogenetics to reverse decreases in alcohol seeking after 5HT2a manipulation to draw causal links. These studies are consistent with the goals of the parent grant, specifically Aim1 which defines neural activity patterns in the CeA, insula, and PVT during ethanol self-administration. As in Aim1, Ms. Castro will utilize in vivo electrophysiology to investigate CeA neural activity, but she focuses on a new angle, that of the effect of serotonin and the 5HT2a receptor. In addition, in Aim3 of the parent grant we use optogenetics to examine manipulation of CeA neural pathways on alcohol self-administration. As with Aim3, Ms. Castro will also use optogenetics to study but here she will test a novel hypothesis that activation of the CeA during a cue will reverse the acute effect of 5HT2a receptor activation. In addition to the focus on the CeA, the proposed supplement studies are consistent with, but not duplicative of, the parent grant because thet use a shared behavioral model, the DT3 seeking-taking procedure that allows isolation of neural process during seeking from those during taking. In Ms. Castro’s case, this will help her understand neurobehavioral mechanisms of 5HT2a receptor modulation. Thus the studies extend the overall goal of the parent grant to better understand CeA mechanisms in alcohol’s effects. Ms. Castro’s studies will complement the overall goal of the parent grant to understand the role of the CeA in alcohol self-administration by providing an independent set of findings. While carrying out her research, Ms. Castro and I will work together to fulfill her goals which include intensive mentoring for oral presentations, manuscript preparations, and submission of an NRSA F31.