Amygdala neural circuits in alcohol intake

项目总结 这一多样性补充应用程序将在两年内支持神经科学研究生Matilde Castro 与支持调查的家长补助金R01-AA027213相关但不多余的培训计划 进入杏仁核和岛叶皮质回路在寻找-服用酒精自我给药的大鼠模型。女士。 卡斯特罗准备进行一段密集的研究期，以获得酒精的神经生物学研究方面的专业知识 动物模型，并在科学和专业研究方面接受高质量的指导。这个 这种强化培训的目的是为卡斯特罗女士的下一步培训做好准备；具体地说，她的数据 在增刊期间取得的成果将：1)构成2-4个第一作者出版物的基础；2)将 为F31申请提供初步数据，从而推动她实现独立 研究生涯。这项投资将对她实现她的研究职业目标和 将使NIH在生物医学研究方面的多样性目标继续向前推进。我们有一条鸿沟 了解了5-羟色胺如何影响CEA与酒精相关的功能，卡斯特罗女士将决定 用电生理学、药理学和神经生物学方法研究CEA中5HT2a受体在酒精寻求/摄取中的作用 光遗传学。在目标1中，她将确定5HT2A受体对CEA神经活动的影响；在目标2中 她将测试微量输注5HT2A激动剂或拮抗剂是否会改变酒精寻求和/或服用；目的 3，她将使用光遗传学来逆转5HT2A操作得出因果关系后寻求酒精的减少 链接。这些研究与父母基金的目标是一致的，特别是Aim1，它定义了神经 乙醇自我给药过程中CEA、脑岛和PVT的活性模式。与Aim1一样，卡斯特罗女士将 利用体内电生理学研究CEA神经活动，但她关注的是一个新的角度，即 5-羟色胺和5-HT2A受体的作用。此外，在家长资助的Aim3中，我们使用光遗传学来 研究CEA神经通路对酒精自我给药的影响。与Aim3一样，卡斯特罗将 也使用光遗传学来研究，但在这里，她将检验一个新的假设，即在提示期间CEA的激活 将逆转5HT2A受体激活的急性效应。除了重点关注CEA外，拟议的 补充研究与父母的资助一致，但不是重复的，因为他们不使用共享的 行为模型，DT3寻找-获取程序，允许在寻找过程中隔离神经过程 从那些在服用过程中。在卡斯特罗女士的案例中，这将帮助她理解 5HT2a受体调控。因此，研究扩展了父母助学金的总体目标，以更好地理解 酒精作用中的CEA机制。卡斯特罗女士的研究将补充父母的总体目标 通过提供一个独立的集合来理解CEA在酒精自我管理中的作用 调查结果。在进行她的研究的同时，我和卡斯特罗女士将共同努力，实现她的目标 包括对口头陈述、手稿准备和提交NRSA F31的密集指导。

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.