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

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH094263-02
Application #
8381855
Study Section
Special Emphasis Panel (ZMH1-ERB-S)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$243,482
Indirect Cost
$57,993
Name
Boston University
Department
Type
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Voss, Joel L; Cohen, Neal J (2017) Hippocampal-cortical contributions to strategic exploration during perceptual discrimination. Hippocampus 27:642-652
Eichenbaum, Howard (2017) Memory: Organization and Control. Annu Rev Psychol 68:19-45
Nilakantan, Aneesha S; Bridge, Donna J; Gagnon, Elise P et al. (2017) Stimulation of the Posterior Cortical-Hippocampal Network Enhances Precision of Memory Recollection. Curr Biol 27:465-470
Riceberg, Justin S; Shapiro, Matthew L (2017) Orbitofrontal Cortex Signals Expected Outcomes with Predictive Codes When Stable Contingencies Promote the Integration of Reward History. J Neurosci 37:2010-2021
Seip-Cammack, Katharine M; Young, James J; Young, Megan E et al. (2017) Partial lesion of the nigrostriatal dopamine pathway in rats impairs egocentric learning but not spatial learning or behavioral flexibility. Behav Neurosci 131:135-42
Guise, Kevin G; Shapiro, Matthew L (2017) Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding. Neuron 94:183-192.e8
Stratton, Peter; Hasselmo, Michael; Milford, Michael (2016) Unlocking neural complexity with a robotic key. J Physiol 594:6559-6567
Eichenbaum, Howard (2016) Still searching for the engram. Learn Behav 44:209-22
Ryals, Anthony J; Rogers, Lynn M; Gross, Evan Z et al. (2016) Associative Recognition Memory Awareness Improved by Theta-Burst Stimulation of Frontopolar Cortex. Cereb Cortex 26:1200-1210
Keene, Christopher S; Bladon, John; McKenzie, Sam et al. (2016) Complementary Functional Organization of Neuronal Activity Patterns in the Perirhinal, Lateral Entorhinal, and Medial Entorhinal Cortices. J Neurosci 36:3660-75

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