The proposed research focuses on development of a detailed and realistic model of how neural firing patterns in the hippocampus, entorhinal cortex, prefrontal cortex and ventral tegmental area mediate goal directed behavior in specific behavioral tasks. These projects explore the interaction of goal activation, response selection and episodic memory for guiding behavior. Understanding these processes of motivated behavior should prove important for understanding the drug addiction processes. In particular this work allows modeling of how alterations in glutamatergic, GABAergic cholinergic and dopaminergic processes within numerous interacting regions could influence addictive behavior. The proposed research will further develop existing software that allows a direct interface between a neural simulation and behavior of a virtual rat in a virtual environment, a model simultaneously constrained by requirements about behavioral function and biologically realistic structure. The neural simulation uses dynamics based on extensive physiological data on rhythmic field potentials (EEG) and firing patterns of individual neurons (unit recording). The research proposed here will involve a continuous interaction between three groups: ? 1. The group in Edinburgh (Robert Cannon and Nigel Goddard) will provide ongoing development of a flexible, graphics based simulation package (CATACOMB), which allows construction of neural simulations for guiding behavior of a virtual rat in a variety of different experimental tasks, including spatial memory tasks and operant tasks. ? 2. The Hasselmo group will continue development of simulations of how the hippocampus, entorhinal cortex, prefrontal cortex and ventral tegmental area are involved in goal directed movements in behavioral tasks. This work will generate clear experimental predictions about the timing of spikes relative o behavior and relative to theta rhythm EEG based on hypotheses about the physiological interaction. ? 3. The Eichenbaum group will analyze data from a spatial alternation task to test specific predictions of the simulation about the timing of spikes during behavior. ? This project will have a synergistic interaction with a separate collaboration between the Hasselmo and Kantak laboratories at B.U., which focuses on modeling operant tasks used in experimental studies of drug self-administration phenomena, in work supported by a supplement to a previous grant from NIDA. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA016454-02
Application #
6668485
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (50))
Program Officer
Volman, Susan
Project Start
2002-09-30
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$243,773
Indirect Cost
Name
Boston University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Hyman, James M; Zilli, Eric A; Paley, Amanda M et al. (2010) Working Memory Performance Correlates with Prefrontal-Hippocampal Theta Interactions but not with Prefrontal Neuron Firing Rates. Front Integr Neurosci 4:2
Yoshida, Motoharu; Hasselmo, Michael E (2009) Persistent firing supported by an intrinsic cellular mechanism in a component of the head direction system. J Neurosci 29:4945-52
Zilli, Eric A; Yoshida, Motoharu; Tahvildari, Babak et al. (2009) Evaluation of the oscillatory interference model of grid cell firing through analysis and measured period variance of some biological oscillators. PLoS Comput Biol 5:e1000573
Giocomo, Lisa M; Hasselmo, Michael E (2008) Time constants of h current in layer ii stellate cells differ along the dorsal to ventral axis of medial entorhinal cortex. J Neurosci 28:9414-25
Hasselmo, Michael E (2008) Neuroscience. The scale of experience. Science 321:46-7
Koene, Randal A; Hasselmo, Michael E (2008) Reversed and forward buffering of behavioral spike sequences enables retrospective and prospective retrieval in hippocampal regions CA3 and CA1. Neural Netw 21:276-88
Zilli, Eric A; Hasselmo, Michael E (2008) The influence of Markov decision process structure on the possible strategic use of working memory and episodic memory. PLoS One 3:e2756
Koene, Randal A; Hasselmo, Michael E (2008) Consequences of parameter differences in a model of short-term persistent spiking buffers provided by pyramidal cells in entorhinal cortex. Brain Res 1202:54-67
Yoshida, Motoharu; Fransen, Erik; Hasselmo, Michael E (2008) mGluR-dependent persistent firing in entorhinal cortex layer III neurons. Eur J Neurosci 28:1116-26
Hasselmo, Michael E (2008) Temporally structured replay of neural activity in a model of entorhinal cortex, hippocampus and postsubiculum. Eur J Neurosci 28:1301-15

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