PROJECT SUMMARY/ABSTRACT Episodic memory is characterized by our ability to remember the spatial and temporal context in which events occur. There is substantial evidence that the hippocampal neuronal activity reflects a representation of space but, until recently, little was known about whether or how the hippocampal neurons encode time. However, recent studies by us have shown that hippocampal neuronal activity provides a temporal context signal that contributes to memory. In addition there is now evidence, substantially accumulated in this project, that hippocampal neurons - called time cells - fire during particular moments in a temporally extended experience, similar to hippocampal place cells that fire associated with particular locations in a spatially extended environment. The proposed studies will continue to explore the nature of temporal representation by the hippocampal system and associated brain areas. Experiments so far have focused on time cell activity during a gap between remembered events in order to identify an unambiguous timing signal in the absence of dynamic external events and while holding place and behavior constant. In the next phase of the project we will explore how time cells organize a sequence of events that compose specific episodes. Also, all recordings of hippocampal time cells have so far been examined only in area CA1. We will examine whether temporal coding is limited to CA1 or widespread in the hippocampus and other medial temporal and prefrontal areas. We will also explore whether temporal sequencing is created within intrinsic hippocampal circuits or whether temporal coding within the hippocampus depends on inputs from cortical areas. These studies will challenge the prevalent view that the hippocampal system is dedicated to spatial navigation and advance our understanding of how this system represents events in their spatiotemporal context.

PROJECT NARRATIVE Our understanding of cognitive disorders, and the eventual development of treatments, depends crucially upon an understanding of the cognitive and neural mechanisms that underlie normal cognition; for example, abnormal thought patterns in schizophrenia, as well as other cognitive disorders, reflects an underlying disorganization of the neural machinery that stores and retrieves memories of our everyday experiences. The proposed work will pioneer a new understanding about how memories are represented in neural circuitry and about how neural representations are organized to guide our retrieval of memories in daily life. Because the hippocampus and adjacent cortical areas are compromised in multiple major mental disorders, an understanding the functional circuitry of these areas is particularly important.