Parabrachial-Forebrain Interactions in CTA

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)的神经基础，这是一种非常重要的学习机制，可以防止反复摄入有毒食物。进化使动物(包括人类)倾向于将胃肠道不适(称为无条件刺激或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这种食物不是导致疾病的原因)可能会对自己的饮食产生强烈的反感(导致食欲不振和厌食症)，因为化疗的不利内脏副作用与他们在治疗前摄入的食物有关。同样，动物在食用食物后昏迷，但如果它们在中毒中幸存下来，则会显示CTA。这些和相关的发现强调了脑干核团在CTA发展过程中的重要性。我们帮助确定臂旁内侧核(MPBN)是获得CTA的一个基本重要区域。我们认为，MPBN在连接味觉CS和厌恶的美国的关联机制中起着至关重要的作用。然而，这一发现表明，慢性丘前去大脑(切断脑干与前脑的连接，同时保持MPBN完整)也阻止了CTA的获得，这表明MPBN并不是单独起作用的：CTA的获得依赖于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获得过程中，哪些前脑结构与MPBN相互作用；(2)这种相互作用的性质是什么？具体目标1将通过关注与MPBN相关的五个脑区来解决第一个问题，在大多数情况下，这些脑区与CTA的某些方面有关：基底外侧杏仁核、杏仁中央核、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，特定的AIMS 2和3将采用先前被证明成功地确定MPBN在CTA中的角色的任务。通过研究与MPBN相关的结构的兴奋性毒性损伤导致的行为障碍，我们希望在确定负责CTA获取的神经系统的长期目标方面取得重大进展。

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.