Memory for the context in which life's events occur is a fundamental component of episodic memory. Also, the use of context representations for memory retrieval, decision-making, and other cognitive functions is disrupted in a number of neurological and neuropsychiatric diseases. Yet, many questions remain about how and where context is represented in the brain. A widespread view of the medial temporal lobe (MTL) memory system posits that object information reaches the hippocampus (HC) via the perirhinal cortex (PER) and spatial information arrives to the hippocampus from the postrhinal cortex (POR). The PER and POR each project to the HC both directly and indirectly through the lateral and medial entorhinal areas. By one view, the spatial pathway conveys both spatial and contextual information to the HC. By another view, the HC, itself, configures spatial and object information into representations of context. Neither view takes into account the robust, multilevel connections across the so-called object and spatial pathways. The proposed studies will resolve these open questions and potentially change how we view information processing in the MTL. The PI will study how MTL structures interact to represent and use object and context information in the service of cognition and behavior. The guiding hypotheses are 1) the POR represents the local spatial context, including the spatial layout of objects, patterns, and featurs of the environment, 2) object and pattern information necessary for context representations arrives to the POR directly from the PER, 3) object-context conjunctive encoding in the HC requires object information from the PER and context representations from the POR, and 4) oscillatory synchrony in the theta frequency band modulates transmission of information among these regions based on task demands, i.e. when spatial, contextual, or object-context conjunctive information is required for task performance. The PI will combine a novel behavioral approach with multisite electrophysiology and optogenetic manipulation in behaving rodents to address these hypotheses. By simultaneously recording and modulating single unit activity and local field potentials in the PER, POR and HC, this work can determine how these structures interact to represent contexts and objects, laying the ground work for understanding how context is represented in the brain and how such representations are used to guide cognition and behavior. The use of contextual representations is disrupted in neuropsychiatric disorders including depression and schizophrenia, and there is associated pathology in the hippocampus and parahippocampal cortex. Understanding how context is represented in the brain and how parahippocampal structures contribute to such representations is important for understanding and treating human mental disorders. These studies will elucidate the neural bases of context and establish an excellent model system for studying context information processing, a core function in human and nonhuman primate brains.

Public Health Relevance

Representations of context are important for perception, memory, decision-making, and other cognitive processes, and there is considerable evidence that the use of contextual representations is disrupted in a number of neuropsychiatric and neurological disorders including Alzheimer's Disease, developmental disorders, schizophrenia, and affective disorders. Many of these disorders are accompanied by changes in the parahippocampal cortex, which is known to contribute to contextual information processing. Understanding how context is represented in the brain and how parahippocampal structures are involved will enhance our understanding and treatment of cognitive symptoms associated with neurological disorders and neuropsychiatric disease.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Neurobiology of Learning and Memory Study Section (LAM)
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Buhring, Bettina D
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Brown University
Social Sciences
Schools of Arts and Sciences
United States
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