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.
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