DESCRIPTION (provided by applicant): A recent convergence of findings in humans and animals indicates that our capacity for episodic memory relies on a system of cortical areas and the hippocampus that encode events in the context in which they occur. To understand the information processing mechanisms that underlie episodic memory, we are pursuing a systems analysis that will compare the nature of information processing and identify functional interactions between cortical and hippocampal areas. In this phase of funding we will focus on the lateral entorhinal cortex (LEC), testing the hypothesis that this area is a critical convergenc site for object and context representation: (1) We will distinguish LEC neural activity with regard to object and context processing and examine whether the nature of this processing has a functional topography. (2) We will characterize interactions between the LEC and interconnected cortical and hippocampal areas, testing the hypothesis that functional interactions develop during the course of learning. (3) We will test whether object and context processing in LEC depend on specific inputs from interconnected cortical and hippocampal areas. Our approach combines a behavioral paradigm for associating events and context, multi-site recording that allows us to identify single neuron and ensemble representation and synchronized activity in multiple areas, and multiple methods of reversible inactivation that identify key interactions between areas. The combined information gained from this systems analysis will improve our model of the functional organization of the cortical-hippocampal system and increase our understanding of how episodic memories are stored and retrieved within this system.

PUBLIC HEALTH RELEVANCE: Our understanding of cognitive disorders and the eventual development of treatments depends crucially upon an understanding of the cognitive and neural mechanisms that underlie normal cognition; for example, abnormal thought patterns in schizophrenia as well as other cognitive disorders reflect an underlying disorganization of the neural machinery that stores and retrieves memories to compose our knowledge of the world. The proposed work will pioneer a new understanding about how memories are represented in neural circuitry and about how neural representations guide cognition in daily life. Because the hippocampus and adjacent cortical areas are compromised in multiple major mental disorders, an understanding of the functional circuitry of these areas is particularly important.