Perirhinal Contributions to Postrhinal Representations of Context

鼻周对环境的鼻后表征的贡献

• 批准号: 9038178
• 负责人: Victoria R. Heimer-McGinn
• 金额: $ 5.61万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-04 至 2017-03-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9038178
• 关键词: Address; Alzheimer' s Disease; Animals; Attention; Behavior; Bilateral; Binding; Boat; Brain; Chloride Ion; Chlorides; Code; Cognition; Cognitive deficits; Complex; Contralateral; Decision Making; Discrimination; Disease; Electrophysiology (science); Environment; Episodic memory; Event; Exhibits; Floor; Halorhodopsins; Hippocampal Formation; Hippocampus (Brain); Human; Image; Implant; Individual; Ipsilateral; Laboratories; Learning; Lesion; Light; Link; Location; Medial; Mental disorders; Monkeys; Mood Disorders; Neurobehavioral Manifestations; Neurons; Neurosciences; Parahippocampal Gyrus; Parietal Lobe; Pattern; Perception; Performance; Play; Primates; Process; Pump; Rattus; Rodent; Role; Schizophrenia; Signal Transduction; Source; Stimulus; Structure; Temporal Lobe; Testing; Viral Vector; Visual; Visual Cortex; base; cognitive function; cognitive process; dentate gyrus; developmental disease; information processing; nervous system disorder; neuropsychiatric disorder; novel; novel therapeutic intervention; object recognition; optical fiber; optogenetics; public health relevance; relating to nervous system; response; social situation

 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.

 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基本功能。因此，在日常观察中，对象通常与上下文环境（例如，炉灶-厨房，船-湖）相关联。语境不仅仅是一个地点，还包括表征特征和对象（例如厨房中的其他电器）。这些语境和客体-语境关联的表征是许多高级认知功能的关键组成部分，包括感知、决策和情景记忆。值得注意的是，在神经和神经精神疾病中，使用背景来指导认知和行为被破坏。尽管情境表征在认知功能、神经系统和神经精神疾病中很重要，但关于这种表征在哪里形成和储存以及它们如何指导行为，还有许多悬而未决的问题。灵长类动物的海马旁皮质（parahippocampal cortex，PHC）或大鼠的同源嗅后皮质（homologous postrhinal cortex，POR）被认为处理来自后顶叶皮质的空间信息，而嗅周皮质（perirhinal cortex，PER）被认为处理来自视觉皮质的物体信息。通过一个视图，项目和上下文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。从另一个角度来看，项目和空间信息在海马体中被配置为表示上下文。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在海马体上游的PHC/POR中形成。事实上，POR神经元已经被证明可以形成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。该应用由总体假设指导，即大鼠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将在行为大鼠中采用实验性损伤、电生理学和光遗传学方法来测试这一假设，其三个相关目的是：1）实验性损伤将用于证实POR和PER之间的连接对于物体-背景识别是必要的; 2）电生理学将用于确定POR神经元是否编码客体-当在新的上下文中遇到熟悉的对象时，上下文连接和信号;以及3）电生理学和光遗传学将用于检查POR中的对象-上下文连接编码是否依赖于来自PER的直接输入。情境表征对于形成情景记忆和基于情境做出决策（例如，如何在不同的社交场合中表现）至关重要。了解背景在大脑中的表现方式和位置，以及背景的表现如何引导行为，将为情景记忆的基础神经科学提供信息。此外，理解上下文处理的神经基础与精神疾病的研究直接相关，并将引导我们走向神经精神疾病认知缺陷的新治疗方法。