Parabrachial-Forebrain Interactions in CTA

CTA 中臂旁前脑相互作用

• 批准号: 7018468
• 负责人: STEPHEN REILLY
• 金额: $ 27.48万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018468
• 关键词: association learning; avoidance behavior; behavior test; behavioral /social science research tag; brain mapping; central neural pathway /tract; conditioning; intercellular connection; laboratory rat; neural information processing; parabrachial nucleus; prosencephalon; taste

DESCRIPTION (provided by applicant): The long term goal of the current proposal is to determine the neural substrates of conditioned taste aversion (CTA), a profoundly important learning mechanism that protects against the repeated ingestion of toxic food. Evolution has predisposed animals (including humans) to associate gastrointestinal malaise (termed the unconditioned stimulus or US) with the taste of the food (the conditioned stimulus or CS). So powerful is this mechanism that cancer patients (despite the fact that they are fully aware that the food did not cause the illness) may develop strong aversions to their diets (leading to a loss of appetite and anorexia) because the adverse visceral side effects of chemotherapy are nonetheless associated with the foods they consumed before treatment. Similarly, animals rendered comatose following consumption of food nevertheless display a CTA if they survive the poisoning. These and related findings emphasize the importance of brainstem nuclei in the development of CTAs. We have helped identify the medial parabrachial nucleus (MPBN) as a fundamentally important area for the acquisition of CTA. We consider that the MPBN is critically involved in the associative mechanism that links the taste CS with the aversive US. However, the finding that chronic precollicular decerebrations (which disconnect the brainstem from the forebrain while leaving the MPBN intact) also prevent the acquisition of CTA, indicates that the MPBN does not work alone: CTA acquisition depends upon an interplay between the MPBN and forebrain structures. Thus, the present proposal seeks answers to the following questions: (1) which forebrain structures interact with the MPBN during CTA acquisition and (2) what is the nature of that interaction? Specific Aim 1 will address the first question by focusing on five brain regions that are connected with the MPBN and, in most cases, have been implicated in some aspect of CTA: the basolateral arnygdala, central nucleus of the amygdala, insular cortex, lateral hypothalamus and the bed nucleus of the stria terminalis. To determine the nature of the MPBN-forebrain interactions, Specific Aims 2 and 3 will employ tasks that have previously proven successful in identifying the role of the MPBN in CTA. By studying the behavioral breakdowns consequent to excitotoxic lesions of structures connected with the MPBN, we expect to make significant progress in our long-term goal of defining the neural system responsible for CTA acquisition.

描述（由申请人提供）：当前提案的长期目标是确定条件性味觉厌恶（CTA）的神经基质，这是一种非常重要的学习机制，可以防止重复摄入有毒食物。进化使动物（包括人类）倾向于将胃肠道不适（称为非条件刺激或US）与食物的味道（条件刺激或CS）联系起来。这种机制如此强大，以至于癌症患者（尽管他们完全意识到食物不会导致疾病）可能会对他们的饮食产生强烈的厌恶（导致食欲不振和厌食），因为癌症患者的不良内脏副作用尽管如此，化疗仍与他们在治疗前食用的食物有关。同样，食用食物后昏迷的动物如果在中毒后幸存下来，仍然会表现出 CTA。这些和相关发现强调了脑干核在 CTA 发育中的重要性。我们帮助将内侧臂旁核 (MPBN) 确定为获取 CTA 的基本重要区域。我们认为 MPBN 关键参与了将品味 CS 与令人厌恶的美国联系起来的联想机制。然而，慢性前脑去脑（使脑干与前脑分离，同时保持 MPBN 完整）也会阻止 CTA 的获得，这表明 MPBN 不能单独工作：CTA 的获得取决于 MPBN 和前脑结构之间的相互作用。因此，本提案寻求以下问题的答案：（1）在 CTA 采集过程中哪些前脑结构与 MPBN 相互作用；（2）这种相互作用的本质是什么？具体目标 1 将通过关注与 MPBN 连接的五个大脑区域来解决第一个问题，这些区域在大多数情况下与 CTA 的某些方面有关：基底外侧杏仁核、杏仁核中央核、岛叶皮质、外侧下丘脑和终纹床核。为了确定 MPBN-前脑相互作用的性质，具体目标 2 和 3 将采用先前已证明成功确定 MPBN 在 CTA 中的作用的任务。通过研究与 MPBN 连接的结构的兴奋性毒性损伤导致的行为崩溃，我们期望在定义负责 CTA 采集的神经系统的长期目标方面取得重大进展。