NEURAL MEDIATION OF CONDITIONED TASTE AVERSIONS

描述（由申请人提供）：行为神经科学的核心问题 神经通路的改变是如何调节持久的行为变化的 参与学习。味觉厌恶条件反射提供了一个很好的模型 来研究学习的神经变化， 可以发生在一个单一的审判，尽管长期拖延之间的条件和 无条件刺激它也是一种学习形式，发生在人类身上， 疾病或疾病治疗的结果，对……有有害影响 胃口拟议的研究是基于细胞群的识别， 味觉厌恶学习过程中激活的神经回路神经激活 将通过免疫染色评估即刻免疫的蛋白质产物。 早期基因c-fos。拟议的研究将解决味觉厌恶和 获取和表达。在解决味觉厌恶表达，研究 将决定孤束核中的细胞是否 在表达投射到脑桥臂旁核期间被激活，和/或 下丘脑的室旁核作为参与回路的一部分 对厌恶的味道产生内脏条件反射。 研究还将确定这些细胞的激活，以及 味觉厌恶的行为表达，需要离散输入 杏仁核和臂旁核。关于味觉厌恶的研究 收购将使用特定蛋白质缺失的敲除小鼠模型 激酶A（PKA）基因。使用特定缺失小鼠的初步研究 R11 B已经证明，这些小鼠不能获得PKA基因， 条件性味觉厌恶并在cFos诱导中显示出特定缺陷 基底外侧杏仁核对氯化锂反应的蛋白质。拟议的研究将 确定是否激活c-fos表达的细胞内， 基底外侧杏仁核对无条件刺激LiCl的反应是 以及所观察到的味觉厌恶缺陷是否 无效突变小鼠的学习仅限于长期，而不是长期。 短期的味觉厌恶记忆其他小鼠品系 与PKA基因的其他选择性缺陷将评估他们的学习 以及基底外侧杏仁核cFos蛋白的诱导。通过定义 条件性味觉厌恶学习的神经通路和细胞类型 该项目将为最终确定 细胞内和细胞间的可塑性变化， 味觉学习

DESCRIPTION (provided by applicant): A central issue in behavioral neuroscience is how alterations in neural pathways mediate the durable behavior changes involved in learning. Taste aversion conditioning provides an excellent model for studying the neural changes which underlie learning because conditioning can occur in a single trial, despite lengthy delays between conditioned and unconditioned stimuli. It is also a form of learning which occurs in humans as a result of illness or treatment for illness, with deleterious effects on appetite. The proposed studies are based on identification of cell groups and neural circuitry activated during taste aversion learning. Neural activation will be assessed by immunostaining for the protein product of the immediate early gene, c-fos. Proposed studies will address both taste aversion acquisition and expression. In addressing taste aversion expression, studies will determine whether cells in the nucleus of the solitary tract which are activated during expression project to the pontine parabrachial nucleus and/or the paraventricular nucleus of the hypothalamus as part of a circuit involved in the generation of visceral conditioned reactions to the aversive taste. Studies will also determine whether activation of these cells, as well as behavioral expression of the taste aversion, require input from discrete regions of amygdala and parabrachial nucleus. Studies addressing taste aversion acquisition will use knockout mouse models with specific deletions of protein kinase A (PKA) genes. Preliminary studies using mice with a specific deletion of a PKA gene, R11B have demonstrated that these mice are unable to acquire a conditioned taste aversion and show a specific defect in the induction of cFos protein in basolateral amygdala in response to LiCl. Proposed studies will determine whether the activation of c-fos expression by cells within the basolateral amygdala, in response to the unconditioned stimulus, LiCl, is required for acquisition and whether the observed defect in taste aversion learning in null mutant mice is limited to the long-term, but not the short-term, version of their taste aversion memory. Additional mouse strains with other selective deficits in PKA genes will be assessed for their learning and the induction of cFos protein in basolateral amygdala. By defining the neural pathways and cell types involved in conditioned taste aversion learning this project will provide the groundwork for eventually characterizing the plastic changes within and between cells which underlie this robust form of gustatory learning.