Amygdala neural circuits in alcohol intake

杏仁核神经回路与酒精摄入量的关系

• 批准号: 10518250
• 负责人: Patricia H. Janak
• 金额: $ 6.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10518250
• 关键词: Acute; Agonist; Alcohol consumption; Alcohols; Amygdaloid structure; Animal Model; Behavioral Model; Biomedical Research; Complement; Cues; Data; Electrophysiology (science); Ethanol; Goals; Individual; Insula of Reil; Investigation; Investments; Link; Manuscripts; Mentors; Modeling; National Research Service Awards; Neural Pathways; Neurobiology; Neurosciences; Oral; Pattern; Pharmacology; Preparation; Procedures; Process; Publications; Rattus; Receptor Activation; Research; Research Training; Role; Self Administration; Serotonin; Testing; Training; Training Programs; United States National Institutes of Health; Work; alcohol effect; alcohol seeking behavior; antagonist; career; data submission; graduate student; in vivo; meetings; neural circuit; neurobehavioral; novel; optogenetics; parent grant; receptor; relating to nervous system; serotonin receptor; Acute; Agonist; Alcohol consumption; Alcohols; Amygdaloid structure; Animal Model; Behavioral Model; Biomedical Research; Complement; Cues; Data; Electrophysiology (science); Ethanol; Goals; Individual; Insula of Reil; Investigation; Investments; Link; Manuscripts; Mentors; Modeling; National Research Service Awards; Neural Pathways; Neurobiology; Neurosciences; Oral; Pattern; Pharmacology; Preparation; Procedures; Process; Publications; Rattus; Receptor Activation; Research; Research Training; Role; Self Administration; Serotonin; Testing; Training; Training Programs; United States National Institutes of Health; Work; alcohol effect; alcohol seeking behavior; antagonist; career; data submission; graduate student; in vivo; meetings; neural circuit; neurobehavioral; novel; optogenetics; parent grant; receptor; relating to nervous system; serotonin receptor

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.

项目摘要 这种多样性补充应用将支持2岁的神经科学研究生Matilde Castro 培训计划与父母赠款R01-AA027213相关但与之相关，该计划支持投资 在寻求酒精自给自足模型的大鼠中，进入杏仁核和绝缘皮层电路。多发性硬化症。 卡斯特罗已经准备好进行大量研究，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心理。这 这种强化培训的目的是为卡斯特罗女士准备培训的下一步。具体来说，她的数据 在补充期间获得的1）构成了2-4个第1作者出版物的基础； 2）会 为F31应用提供初步数据，从而促使她进入她的独立性 研究职业。这项投资将使她有价值地实现她的研究职业目标和 将能够持续发展生物医学研究多样性目标的NIH目标。我们有差距 了解5-羟色胺如何影响CEA的酒精相关功能，Castro女士将确定 5HT2A受体在CEA中的作用在酒精寻求/服用，使用电生理学，药理学和 光遗传学。在AIM 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5HT2A激动剂或拮抗剂的微灌注是否会改变寻求和/或服用的酒精；目标 3，她将使用光遗传学在5HT2A操纵后逆转饮酒以逆转下降以吸引因果关系 链接。这些研究与父母赠款的目标一致，特别是AIM1，该目标定义了中立 乙醇自我给药期间CEA，绝缘和PVT中的活动模式。与AIM1一样，卡斯特罗女士将 利用体内电生理学研究CEA神经元活动，但她专注于一个新角度 5-羟色胺和5HT2A受体的影响。此外，在父母赠款的AIM3中，我们使用光遗传学 检查对酒精自我管理的CEA神经途径的操纵。与AIM3一样，卡斯特罗女士将 还使用光遗传学研究，但在这里她将测试一个新的假设，即在提示过程中激活CEA 将逆转5HT2A受体激活的急性效应。除了对CEA的关注，提议 补充研究与父母的赠款一致但不一定，因为他们使用共享 行为模型，DT3寻求采用程序，允许在寻求过程中隔离神经过程 从那些服用期间。在卡斯特罗女士的情况下，这将有助于她了解神经行为机制 5HT2A受体调制。研究扩展了父母赠款的总体目标，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完成父母的总体目标 授予通过提供独立集合来了解CEA在酒精自我管理中的作用 发现。在进行研究时，卡斯特罗女士和我将共同实现她的目标 包括针对口头演示的强化心理，手稿准备以及提交NRSA F31。