GUSTATORY AVERSIONS AND THE PARABRACHIAL NUCLEUS

描述：调查人员断言，对 味觉刺激是味觉三个过程之间复杂的相互作用 新恐惧症，定义为对新奇口味的天生恐惧，胃肠道 不适，这是一种正常现象，发生在摄入 有毒物质和学习，味觉之间的联系 和不适。研究人员选择了条件性的味觉厌恶 (CTA)范式作为模型，现在建议调查 CTA学习中的臂旁核(PBN)。PBN在战略上 在此响应中很重要，因为它似乎是 通过脑干参与的上升和下降通路 味觉和内脏传入系统。在以前的工作中， 调查人员复制并扩展了其他人的工作，表明 PBN病变破坏了动物形成CTA的能力。重要的是，他 还发现，PBN损伤似乎可以消除味觉新恐惧症，以及 他认为，非新恐惧症动物不能形成CTA，因为 他们并不认为新奇的口味有潜在的危险。因此，他 假设PBN损毁的大鼠明显不能形成 CTA，而不是由于无法形成联想 品味和有害事件之间的联系，实际上是由于 病变导致对品尝者的误解。在这方面，它是好的。 确定完整的动物不容易形成熟悉的CTA (即已知是安全的)品尝者。 拟议的实验将使用鹅掌酸损伤选定的区域 PBN来测试这一假设的各个方面。在一系列 实验中，患有PBN损伤的动物将被评估为新的恐惧症 包括几个品尝者的各种刺激，假设是 这样的动物会有一种普遍的新恐惧症缺陷。非- 除了几个品尝者外，还将使用味觉刺激。在其他 实验中，PBNx动物感知味觉的能力将是 评估，以及他们适当反应的能力(即 对品尝者表现出“警觉反应”)。在另一个系列中 实验表明，PBN受损的动物将受到更多 开发CTA的严格和更长的协议， 假设需要同样的努力才能形成一个 PBNx大鼠对一种新口味的厌恶通常需要形成 对控制中熟悉的品尝者的厌恶。最后，调查员 对于不同的品尝者，主题的相对熟悉度会有所不同 在试图对厌恶进行条件调整以最大化或 尽量减少PBNx和对照动物之间的差异。 在所有提议的实验和范例中，将有一个 评估以下两个主要司的相对贡献 PBN。内侧臂旁核为味觉部，外侧臂旁核为味觉部 内脏传入部分。因此，所有实验都将运行 同时，一只手臂调查内侧，另一只手臂调查 侧向PBN。对于大多数情况，调查员还将包括 对急性(即15分钟)和24小时摄入量的评估 评估短期的味觉和进食后的影响。 在试点工作中，调查员既证明了缺乏 内侧PBNx大鼠的新恐惧症及其(尽管减弱)能力 组建一个CTA。他还复制了其他人的影响 PBN的电解性损害，并获得了与 局部使用鹅膏糖酸。他还提供了PBNx大鼠 可以区分品尝者，他们体验到了急性毒性 氯化锂的影响。

DESCRIPTION: The investigator asserts that the ingestive reaction to taste stimuli is a complex interaction among three processes, taste neophobia, defined as an innate fear of novel tastes, gastrointestinal malaise, a normal phenomenon that occurs following ingestion of poisonous substances, and learning, the associative link between taste and malaise. The investigator has chosen the conditioned taste aversion (CTA) paradigm as a model and now proposes to investigate the role of the parabrachial nuclei (PBN) in CTA learning. The PBN is strategically important in this response because it appears to be part of both the ascending and the descending pathways through the brainstem involved in the gustatory and visceral afferent systems. In previous work, the investigator has replicated and extended the work of others showing that PBN lesions disrupt the ability of animals to form CTAs. Importantly, he has also found that PBN lesions appear to abolish taste neophobia, and he argues that non-neophobic animals are not able to form CTAs because they do not perceive novel tastes as potentially dangerous. He therefore hypothesizes that the apparent inability of PBN-lesioned rats to form a CTA, rather than being due to an inability to form associative connections between tastes and noxious events, is actually due to a lesion-induced misperception of the tastant. In this regard, it is well established that intact animals do not easily form CTAs well to familiar (i.e., known to be safe) tastants. Proposed experiments will use ibotenic acid lesions of selected areas of the PBN to test various aspects of this hypothesis. In one series of experiments, animals with PBN lesions will be assessed for neophobia to a variety of stimuli including several tastants, the hypothesis being that such animals will have a generalized neophobic deficit. Non- gustatory stimuli will be used in addition to several tastants. In other experiments, the ability of PBNx animals to perceive tastants will be assessed, as will their ability to react appropriately (i.e., to demonstrate an "alerting response") to the tastants. In another series of experiments, animals with PBN lesions will be subjected to more rigorous and more prolonged protocols for developing CTAs, the hypothesis being that the same effort will be required to form an aversion to a novel tastant in PBNx rats as is normally required to form an aversion to a familiar tastant in controls. Finally, the investigator will vary the relative familiarity of the subjects to various tastants prior to attempting to condition aversions in order to maximize or minimize the differences between PBNx and control animals. In all of the proposed experiments and paradigms, there will be an assessment of the relative contributions of the two major divisions of the PBN. The medial PBN is the gustatory portion and the lateral PBN is the visceral afferent portion. Therefore, all experiments will be run in parallel, with one arm investigating the medial and the other the lateral PBN. For most conditions the investigator will also include assessments of both acute (i.e., 15-minute) and 24-hour intakes to assess both short-term gustatory and post-ingestive influences. In pilot work, the investigator has demonstrated both the lack of neophobia in medial PBNx rats, and their (albeit lessened) ability to form a CTA. He has also replicated the effects of others with electrolytic lesions of the PBN and obtained comparable findings with locally applied ibotenic acid. He has also provided data that PBNx rats can discriminate tastants, and that they experience the acute toxic effects of lithium chloride.