Computational models of the hippocampal formation, entorhinal cortex and prefrontal cortex will be used to simulate memory-guided behavior in both rat and human behavioral tasks. These simulations will extend previous 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 predictions about physiological data in a range of different memory-guided tasks. Selection of behavioral actions in the model 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 theta rhythm during performance of the order recognition task with odors in rats, and the magnitude of fMRI activation associated with correct versus incorrect performance of an order recognition task in humans, 2.) generation of predictions about context-dependent properties and theta phase of neuronal firing in the odor sequence disambiguation task, and the magnitude of fMRI activation associated 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 and behavior and the disruption of behavioral responses caused by stimulation at different phases of theta during different task periods. These simulations will use networks of neurons starting with threshold units and building to use of detailed compartmental biophysical simulations, to relate network dynamics to intrinsic currents and subclasses of neurons within the hippocampus and entorhinal cortex. The insights gained from this work will improve our understanding of the normal function of the hippocampus and associated cortex, potentially contributing to treatment of memory impairments in disorders such as Alzheimer's disease or schizophrenia.
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