This project will develop a shared computational model to identify unified mechanisms for interactions of the prefrontal cortex (PFC) and medial temporal lobe cortex (MTL) in the performance of a behavioral task requiring cued responses based on context.
The specific aims focus on modeling the properties of timing of neural spiking activity in PFC and MTL during performance of related behavioral tasks in rodents in Project 4-5, and on the properties of neural spiking in monkeys in Project 3 and the magnitude of functional magnetic resonance imaging (fMRI) activity in humans in Projects 1-2. In addition, the specific aims will address the effect of the damage to different cortical regions on behavioral performance and measures of neural activity. Based on previous models from this lab, network models of integrate-and-fire neurons or biophysical compartmental simulations representing subregions of the PFC and MTL will be used to generate predictions about experimental data that will guide data analysis, and comparison with the data will determine whether features of the shared model are retained or restructured to account for the data. Modeling predictions will address relative timing of unit activity between regions and timing relative to network oscillations in Projects 4-5, and experimental outcomes will guide selection of neural mechanisms for representation of context, such as oscillatory interference or the temporal context model. Models will generate predictions about the relative timing of unit activity in monkeys in Project 3, and the magnitude of fMRI activity and patterns of preferential viewing in humans in Projects 1 and 2 before and after the transition to context-based responding, and during inferences to cues presented in novel quadrants. The outcomes of these comparisons to data will guide extension of the model to address human and monkey PFC-MTL interactions in relation to rodents.

Public Health Relevance

Impairments of PFC function are implicated in mental disorders, including schizophrenia and depression, and these disorders are also associated with pathological changes in the MTL. Modeling PFC-MTL interactions between provides a theoretical framework for addressing pathological changes in these interactions that contribute to the progression of degenerative mental disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH094263-02
Application #
8381859
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
$216,642
Indirect Cost
$47,551
Name
Boston University
Department
Type
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Rueckemann, Jon W; DiMauro, Audrey J; Rangel, Lara M et al. (2016) Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons. Hippocampus 26:246-60
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 26:1200-10
Place, Ryan; Farovik, Anja; Brockmann, Marco et al. (2016) Bidirectional prefrontal-hippocampal interactions support context-guided memory. Nat Neurosci 19:992-4
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
Eichenbaum, Howard (2016) Still searching for the engram. Learn Behav 44:209-22
McKenzie, Sam; Keene, Christopher S; Farovik, Anja et al. (2016) Representation of memories in the cortical-hippocampal system: Results from the application of population similarity analyses. Neurobiol Learn Mem 134 Pt A:178-91
Chen, Zetao; Lowry, Stephanie; Jacobson, Adam et al. (2015) Bio-inspired homogeneous multi-scale place recognition. Neural Netw 72:48-61
Wang, Jane X; Voss, Joel L (2015) Long-lasting enhancements of memory and hippocampal-cortical functional connectivity following multiple-day targeted noninvasive stimulation. Hippocampus 25:877-83
Howard, Marc W; Eichenbaum, Howard (2015) Time and space in the hippocampus. Brain Res 1621:345-54
Puig, M Victoria; Miller, Earl K (2015) Neural Substrates of Dopamine D2 Receptor Modulated Executive Functions in the Monkey Prefrontal Cortex. Cereb Cortex 25:2980-7

Showing the most recent 10 out of 55 publications