This project will employ a combination of recording and reversible inactivation techniques to examine how PFC and MTL areas interact in rats performing a context-guided association task that is formally equivalent to the test used in humans and monkeys in other projects. In this task, on each trial a rat will be move into one of two environmental contexts that conditions associations between odor stimulis and rewards. Using multichannel tetrodes, we will record simultaneously in an MTL area and a PFC area, and test specific hypotheses outlined about the development, nature, timing, and coordination of firing patterns in these areas. These studies will test the generality of our overall hypotheses about information processing in PFC and MTL areas in rats as compared to those in humans and monkeys examined in Projects 1-3. We will also go beyond identifying functional properties of neuronal activity in other experiments by simultaneously recording in one area while reversibly inactivating another area for brief periods during and after learning. Reversible inactivation will be accomplished using florescent muscimoi and by state-of-the-art optical silencing methods that allow millisecond resolution of anatomically identified areas. These experiments will provide tests of whether firing patterns normally observed in one area depend on the other. For example, we will test the hypothesis that, during learning, the development of context general representations in PFC depend on specific MTL areas;whether, within trials following learning, the generation of specific context representations in postrhinal/medial entorhinal cortex depends on PFC;and whether the generation of specific representations of the second element on a conditional association in PFC depends on perirhinal cortex. These and other specific tests will provide evidence on causal relations among areas within PFCMTL circuitry, providing key evidence for computational modeling in Project 6. This project will closely parallel Project 5, which examines the nature of PFC-MTL interactions in rats performing a similar context guided spatial maze task, thus allowing direct comparisons that link the PFC-MTL processing of non-spatial memorties with the large literature on hippocampal spatial memory.

Public Health Relevance

By close coordination and integration with other projects, we will validate the use of rodent models of human PFC-MTL interactions for studies directed at understanding the origins of mental disorders. In addition, this project will provide a new model of PFC-MTL function in the neural basis of cognition that can be applied to examine the effects of potential therapies at the level of neural information processing

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1-ERB-S)
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Boston University
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Howard, Marc W; Eichenbaum, Howard (2015) Time and space in the hippocampus. Brain Res 1621:345-54
Wang, Jane X; Cohen, Neal J; Voss, Joel L (2015) Covert rapid action-memory simulation (CRAMS): a hypothesis of hippocampal-prefrontal interactions for adaptive behavior. Neurobiol Learn Mem 117:22-33
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