Perirhinal Contributions to Postrhinal Representations of Context

 描述(由申请人提供)：解释和使用环境背景来告知认知过程和指导行为的能力是人脑的一项基本功能。因此，在日常观察中，物体通常与背景环境(例如炉灶-厨房、船-湖)联系在一起。语境不仅仅是一个地方，还包括表征特征和物体(例如厨房里的其他电器)。这些对语境和对象-语境关联的表征是许多高级认知功能的关键组成部分，包括知觉、决策和情景记忆。值得注意的是，在神经性和神经精神障碍中，使用情境来指导认知和行为是被破坏的。尽管语境表征在认知功能以及神经和神经精神疾病中的重要性，但关于这种表征是在哪里形成和存储的，以及它们如何指导行为，仍有许多悬而未决的问题。灵长类动物的海马旁皮质(PHC)或大鼠的同源后皮质(POR)被认为处理从后顶叶皮质接收的空间信息，而周围皮质(PER)被认为处理来自视觉皮质的物体信息。根据一种观点，项目和背景信息分别到达海马体，并在那里整合，形成事件和情节的表示。根据另一种观点，海马体中的项目和空间信息被配置为代表上下文。然而，最近对大鼠、猴子和人类的研究提供了证据，表明背景的表征可能是在海马体上游的PHC/POR形成的。事实上，POR神经元已经被证明形成了将物体与地点联系起来的表征，这是环境背景复杂表征的重要组成部分。这一应用是由总体假设指导的，即RAT POR将空间信息与从PER接收的对象信息相结合，以形成上下文的复杂表示，包括局部环境中对象和特征的空间布局。PI将使用实验损伤、电生理学和光遗传学方法对大鼠的行为进行测试，以验证这一假说有三个相关目的：1)实验损伤将被用来确认POR和PER之间的连接对于物体-语境识别是必要的；2)电生理学将被用来确定当在新的语境中遇到熟悉的物体时，POR神经元是否编码对象-语境连接和信号；以及3)电生理学和光遗传学将被用来检查POR中的对象-语境连接编码是否依赖于PER的直接输入。语境的表征对于形成情景记忆和根据语境做出决定(例如，如何在不同的社会情境中表现)是必不可少的。理解背景在大脑中如何以及在哪里表现，以及背景引导行为的表现将为情景记忆的基础神经科学提供信息。此外，理解语境加工的神经基础与精神疾病的研究直接相关，并将引导我们寻找治疗神经精神疾病认知缺陷的新方法。

 DESCRIPTION (provided by applicant): The ability to interpret and use environmental context to inform cognitive processes and guide behavior is an essential function of the human brain. Accordingly, in everyday observation, objects are commonly linked to a contextual setting (e.g. stove-kitchen, boat-lake). Context is not simply a place but also includes characterizing features and objects (e.g. other appliances in the kitchen). These representations of context and object-context associations are a key component of many higher cognitive functions including perception, decision-making, and episodic memory. Notably, the use of context to guide cognition and behavior is disrupted in neurological and neuropsychiatric disorders. Despite the importance of contextual representations in cognitive function and neurological and neuropsychiatric disease, there are many open questions about where such representations are formed and stored and how they guide behavior. The parahippocampal cortex (PHC) in primates, or the homologous postrhinal cortex (POR) in rats, is thought to process spatial information received from the posterior parietal cortex, whereas the perirhinal cortex (PER) is known to process object information from the visual cortex. By one view, item and context information arrive separately to the hippocampus and are integrated there to form representations of events and episodes. By another view, item and spatial information are configured in the hippocampus to represent context. Recent studies in rats, monkeys and humans, however, provide evidence that representations of context may be formed in the PHC/POR, upstream of the hippocampus. Indeed, POR neurons have been shown to form representations that link objects to places, an essential component of complex representations of environmental context. This application is guided by the overarching hypothesis that the rat POR combines spatial information with object information received from the PER to form complex representations of context, including the spatial layout of objects and features in the local environment. The PI will employ experimental lesion, electrophysiology, and optogenetic approaches in behaving rats to test this hypothesis in three related aims: 1) experimental lesions will be used to confirm that connections between the POR and the PER are necessary for object-context recognition; 2) electrophysiology will be used to determine whether POR neurons encode object-context conjunctions and signal when a familiar object is encountered in a new context; and 3) electrophysiology and optogenetics will be used to examine whether object-context conjunctive coding in the POR relies on direct input from the PER. Representations of context are essential to form episodic memories and to make decisions based on context (e.g. how to behave in different social situations). Understanding how and where context is represented in the brain and how representations of context guide behavior will inform the basic neuroscience of episodic memory. In addition, understanding the neural basis of contextual processing is directly relevant to the study of mental illness and will steer us towards novel therapeutic approaches for the cognitive deficits in neuropsychiatric disease.