Program Director/Principal Investigator (Last, First, Mlddle): Howard, Marc PROJECT SUMMARY (See lnstrucUons): In recent years, the role of the hippocampal place cell system in constructing a .. map" of a spatial environment has received a great deal of attention, including a Nobel Prize In 2014. However, a close examination of the firing of neurons in the place cell system reveals a more general function, providing a map of "memory space" that includes information not only about spatial coordinates, but also about objects in space and reward contingencies. Moreover, empirical work suggests that the hippocampal theta rhythm provides a mechanism for animals to imagine possible future paths to construct appropriate decisions. Using a combination of empirical work, advanced data analyses and computational modeling, this proposal develops a hypothesis for how the hippocampus and frontal cortex cooperate to navigate this general memory space to inform future behavior. Studies of amnesia patients have made it clear that the hippocampus is important in both memory for the past and imagination for the future. Although a great deal is known about the spatial responsiveness of place cells in the hippocampus, it is not clear how those findings bear on the question of memory-the primary cognitive function of the hippocampus. This proposal builds bridges between the spatial function of the hippocampus and memory by building a computational model for both memory for the past and imagination of the future in a general memory space. The project bridges levels of decription from behavior, to an abstract mathematical framework, to systems neuroscience. Advanced data analytic techniques will be used to test specific predictions of the computational model regarding changes in firing rate and firing relative to ongoing theta oscillations. Finally a novel series of experiments will build a bridge in our understanding of the cooperative role of the hippocampus and orbitofrontal cortex in remembering the past and anticipating the future. RELEVANCE (See instructions): The proposed research may shed new light on disorders associated with changes in temporal discounting, including addiction, ADHD, schizophrenia and bipolar disorder. Moreover, because the computational model relates low-level neurophysiological phenomena with a cognitive-level function, this approach may enable us to better anticipate the effect of pharmacological agents on cognition.