The neural basis of spatial context.

描述(申请人提供)：我们对日常事件的有意识记忆(即情节记忆)是由我们多年来经历的许多人、地点和事情之间的无数联系组成的。这种记忆是由海马体记忆系统支持的，也被称为内侧颞叶记忆系统。构成海马体记忆系统的结构，包括海马体结构和海马旁区域，在灵长类和啮齿类动物之间显示出显著的连接和功能同源性。因此，啮齿动物为研究人类记忆提供了一个很好的动物模型。目前，关于海马区和副海马区内的单个结构如何参与情景记忆，存在很大的分歧。这项拟议的研究将使用大鼠模型来检验两个海马旁区域对记忆的贡献，即海马区后皮质(POR；啮齿动物与灵长类副海马区同源)和海马周皮质(PER)。POR被认为参与了空间/语境信息的处理，而PER在处理物体信息方面起着公认的作用。然而，这两个地区之间的相互作用还没有被很好地理解。我的指导性假设是，POR和PER之间的直接联系为关联表征提供了神经回路，将个别物品与位置联系起来。具体目标将使用一种新的行为仪器来检验这一假设的三个关键方面：1)POR和PER都是将对象与地点联系起来的关联表征所必需的；2)对象-语境关联是在海马体的上游形成的；以及3)在PER和POR中都会观察到对象-上下文关联的神经关联。实验1和2将采用损伤和失活分析来确定PER和POR是否分别是处理2D视觉“物体”和有图案的地板背景所必需的，以及链接项目和上下文的关联是否在海马体上游形成。在实验3中，将记录单个单位的活动和局部场电位，以检验POR和PER中的神经活动与需要对项目和上下文进行加工的任务的成绩的相关性。如果完成，这些实验将更深入地了解空间语境在情景记忆中的作用，包括语境在哪里被表征，以及这种表征如何影响记忆的其他方面，例如识别和提取。对这些问题的更好理解不仅有助于我们对记忆的基本理解，而且有可能改进与脑创伤或疾病相关的记忆障碍的治疗，例如阿尔茨海默病、癫痫和精神分裂症。

DESCRIPTION (provided by applicant):Our conscious memories of daily events (i.e. episodic memory) are made of up countless associations among the many people, places, and things we have experienced over the years. This sort of memory is supported by the hippocampal memory system, also called the medial temporal lobe memory system. The structures that compose the hippocampal memory system, including the hippocampal formation and parahippocampal regions, display remarkable connectional and functional homology between primates and rodents. Thus, rodents provide an excellent animal model for studying human memory. Currently, there is substantial disagreement about how individual structures within the hippocampal and parahippocampal regions are involved in episodic memory. The proposed studies will employ a rat model to examine the contributions of two parahippocampal regions to memory, the postrhinal cortex (POR;rodent homolog to primate parahippocampal cortex) and the perirhinal cortex (PER). POR is thought to be involved in processing spatial/contextual information and PER has an identified role in processing object information. The interactions between the two regions, however, are not well understood. My guiding hypothesis is that the direct connections between the POR and PER provide the neural circuitry for associative representations that link individual items to locations. The specific aims will employ a novel behavioral apparatus to test three key aspects of this hypothesis:1) both the POR and the PER are necessary for associative representations that link objects to places, 2) object-context associations are formed upstream of the hippocampus, and 3) neural correlates of object-context associations will be observed in both PER and POR. Experiments 1 and 2 will employ lesion and inactivation analysis to determine if the PER and POR are necessary for processing 2D visual "objects" and patterned floor backgrounds, respectively, and whether associations that link items and context are formed upstream of the hippocampus. In Experiment 3, single unit activity and local field potentials will be recorded to examine correlates of neural activity in the POR and PER with performance on a task that requires processing of items and contexts. If completed, these experiments will provide greater insight into the role of spatial context in episodic memory, including where context is represented, and how such representations influence other aspects of memory, for example recognition and retrieval. A better understanding of these issues will not only inform our basic understanding of memory, but has the potential to improve treatment of memory impairments associated with brain trauma or disease,e.g. Alzheimer's Disease, epilepsy, and schizophrenia.