Episodic memory involves binding stimuli and/or events together in time and place. Furthermore, memories become more complex when new experiences influence the meaning of stimuli within the original memory. Thus collectively, complex episodic memory formation and maintenance involves processes such as encoding, storage, retrieval, updating and reconsolidation, which can be studied using animal models of higher-order conditioning. In the present study aversive and appetitive sensory preconditioning paradigms were used to test the hypothesis that the postrhinal cortex (POR), which is a component of the hippocampal memory system, is involved in higher-order conditioning. Drawing on the known role of the POR in contextual learning, Experiment 1 employed a four-phase sensory preconditioning task that involved fear learning and context discrimination in rats with or without permanent lesions of the POR. In parallel, to examine POR function during higher-order conditioning in the absence of a particular spatial arrangement, Experiments 2 and 3 used a three-phase sensory preconditioning paradigm involving phasic stimuli. In Experiment 2, bilateral lesions of the POR were made and in Experiment 3, a chemogenetic approach was used to temporarily inactivate POR neurons during each phase of the paradigm. Evidence of successful sensory preconditioning was observed in sham rats which, during the critical context discrimination test, demonstrated higher levels of freezing behavior when re-exposed to the paired versus the unpaired context, whereas POR-lesioned rats did not. Data from the appetitive sensory preconditioning paradigm also confirmed the hypothesis in that during the critical auditory discrimination test, sham rats showed greater food cup responding following presentations of the paired compared to the unpaired auditory stimulus, whereas POR-lesioned rats did not. Lastly, in Experiment 3, when the POR was inactivated only during preconditioning or only during conditioning, discrimination during the critical auditory test was impaired. Thus, regardless of whether stimulus-stimulus associations were formed between static or phasic stimuli or whether revaluation of the paired stimulus occurred through association with an aversive or an appetitive unconditioned stimulus, the effects were the same; POR lesions disrupted the ability to use higher-order conditioned stimuli to guide prospective behavior.

情景记忆涉及在时间和地点上将刺激和/或事件结合在一起。此外，当新体验影响原始记忆中刺激的意义时，记忆会变得更加复杂。因此，总的来说，复杂的情景记忆形成和维持涉及编码、存储、检索、更新和重新巩固等过程，可以使用高阶条件反射的动物模型进行研究。在本研究中，厌恶和食欲感觉预处理范式用于检验作为海马记忆系统的组成部分的鼻后皮层 (POR) 参与高阶条件反射的假设。借鉴 POR 在情境学习中的已知作用，实验 1 采用了一个四阶段的感觉预处理任务，包括在有或没有 POR 永久性损伤的大鼠中进行恐惧学习和情境辨别。同时，为了在没有特定空间排列的情况下检查高阶调节期间的 POR 功能，实验 2 和 3 使用了涉及相位刺激的三相感觉预处理范例。在实验 2 中，制造了 POR 的双侧损伤，在实验 3 中，在范式的每个阶段使用化学遗传学方法暂时灭活 POR 神经元。在假大鼠中观察到成功的感觉预处理的证据，在关键环境辨别测试期间，当重新暴露于配对环境与未配对环境时，表现出更高水平的冻结行为，而 POR 损伤大鼠则没有。来自食欲感觉预处理范式的数据也证实了这一假设，即在关键的听觉辨别测试中，与未配对的听觉刺激相比，假大鼠在配对的呈现后表现出更大的食物杯反应，而 POR 损伤的大鼠则没有。最后，在实验 3 中，当 POR 仅在预调节期间或仅在调节期间失活时，关键听觉测试期间的辨别力受损。因此，无论是在静态或阶段性刺激之间形成刺激-刺激关联，还是通过与厌恶性或食欲性无条件刺激相关联而对配对刺激进行重估，效果都是相同的。POR 损伤破坏了使用高阶条件刺激来指导预期行为的能力。