Computational models of the hippocampal formation, entorhinal cortex and prefrontal cortex will be used tosimulate memory-guided behavior in both rat and human behavioral tasks. These simulations will extendprevious modeling work in this laboratory (Hasselmo et al., 2002b; Fransen et al., 2002; Koene et al., 2003;Hasselmo, 2005a; Koene and Hasselmo, 2005; Hasselmo and Eichenbaum, 2005) to generate predictionsabout physiological data in a range of different memory-guided tasks. Selection of behavioral actions in themodel depends on the encoding and context dependent retrieval of sequences of input stimuli (i.e.episodes). The models will generate predictions for specific research projects in the center, including:1.) generation of predictions about the timing of neuron firing relative to stimuli and hippocampal thetarhythm during performance of the order recognition task with odors in rats, and themagnitude of fMRI activation associated with correct versus incorrect performance of an order recognitiontask in humans,2.) generation of predictions about context-dependent properties and theta phase of neuronal firing in theodor sequence disambiguation task, and the magnitude of fMRI activationassociated with choice in a disambiguation task in humans,3.) generation of predictions about the delayed non-match to place (DNMP) task in the T-maze, concerning the timing of splitter cell responses and sequence readout relative to theta rhythm andbehavior and the disruption of behavioral responses caused by stimulation at different phases of theta duringdifferent task periods.These simulations will use networks of neurons starting with threshold units and building to use of detailedcompartmental biophysical simulations, to relate network dynamics to intrinsic currents and subclasses ofneurons within the hippocampus and entorhinal cortex. The insights gained from this work will improve ourunderstanding of the normal function of the hippocampus and associated cortex, potentially contributing totreatment of memory impairments in disorders such as Alzheimer's disease or schizophrenia.
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