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）的神经底物，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。这种机制是如此强大，以至于癌症患者（尽管他们完全意识到食物不是导致疾病的原因）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症），因为化疗的不良内脏副作用仍然与他们在治疗前食用的食物有关。同样，动物在食用食物后陷入昏迷，但如果它们在中毒后幸存下来，就会显示CTA。这些和相关的发现强调了脑干核在cta发展中的重要性。我们已经帮助确定内侧臂旁核（MPBN）作为CTA获取的一个基本重要区域。我们认为MPBN在连接味觉CS和厌恶US的联想机制中起关键作用。然而，慢性前丘性失觉（断开脑干与前脑的连接，同时保留MPBN的完整）也会阻止CTA的获取，这表明MPBN并不是单独起作用的：CTA的获取取决于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获取期间，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相关的五个大脑区域来解决第一个问题，在大多数情况下，这些区域与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将采用先前已被证明在确定MPBN在CTA中的作用方面成功的任务。通过研究与MPBN相连的结构的兴奋性毒性病变导致的行为障碍，我们期望在定义负责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.