Amygdala neural circuits in alcohol intake

点击翻译按钮获取中文摘要

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.