Episodic memory includes the capacity to internally re-experience the sequence of events that occurred at particular places and times, in what has been termed “mental time travel” (Eichenbaum and Cohen, 2001, Tulving, 2001 and Tulving, 2002). Episodic memory includes the capacity to mentally retrace trajectories through previously visited locations, including re-experiencing specific stimuli encountered on this trajectory, and the relative timing of events. For example, you can probably remember the route you followed when you left your home this morning, with a memory of the locations you visited and the time you spent in individual locations. You can use this memory to remember where you parked the car, who you saw on your trip, or where you left your car keys. This aspect of episodic memory requires some means by which neurons can code continuous trajectories through space with time intervals representing the original episode. This also requires some means for encoding the location and time of specific events or stimuli encountered along this trajectory.
Physiological data shows that hippocampal activity during REM sleep can replay the relative time intervals of spiking activity evoked by different spatial locations during waking (Louie & Wilson, 2001), indicating the capacity to replay spatiotemporal trajectories with the same time scale as actual behavior. Other experiments also show that spiking activity in the hippocampal formation can maintain information about the relative timing of events (Berger et al., 1983, Deadwyler and Hampson, 2006 and Hoehler and Thompson, 1980).
Lesion data suggests that encoding and retrieval of previously experienced episodic trajectories involves the entorhinal cortex and hippocampus. In humans, lesions of these structures cause profound impairments of episodic memory, tested both qualitatively and with quantitative measures in verbal memory tasks (Corkin, 1984, Eichenbaum and Cohen, 2003, Graf et al., 1984, Rempel-Clower et al., 1996 and Scoville and Milner, 1957). Impairments in formation of object-location associations occur with right hippocampal or parahippocampal lesions (Bohbot et al., 2000, Bohbot et al., 1998, Milner et al., 1997 and Stepankova et al., 2004). In rats, hippocampal manipulations impair performance in tasks that can be solved using episodic retrieval of specific recent trajectories, including the 8-arm radial maze (Bunce, Sabolek, & Chrobak, 2004), delayed spatial alternation (Ennaceur, Neave, & Aggleton, 1996), the Morris water maze with new platform location on each day (Buresova et al., 1986 and Steele and Morris, 1999) and a task testing a sequence of spatial locations (Lee, Jerman, & Kesner, 2005). Spatial memory is also impaired by lesions of the entorhinal cortex (Steffenach, Witter, Moser, & Moser, 2005) and postsubiculum (Taube, Kesslak, & Cotman, 1992). Learning of spatial trajectories may be a special case of a general capacity for learning sequences within the hippocampus (Eichenbaum, Dudchenko, Wood, Shapiro, & Tanila, 1999), including the sequential order of sensory stimuli (Agster et al., 2002, Fortin et al., 2002, Kesner et al., 2002 and Kesner and Novak, 1982).
Many previous models of hippocampal function focus on its role in spatial navigation to goals (Burgess et al., 1997, Foster et al., 2000, Touretzky and Redish, 1996 and Trullier and Meyer, 2000), but not on episodic retrieval of specific trajectories. Most previous hippocampal models that focus on encoding and retrieval of sequences (Hasselmo and Eichenbaum, 2005, Jensen and Lisman, 1996a, Jensen and Lisman, 1996b, Levy, 1996, McNaughton and Morris, 1987, Minai and Levy, 1993, Redish and Touretzky, 1998, Treves and Rolls, 1994, Tsodyks et al., 1996, Wallenstein and Hasselmo, 1997 and Zilli and Hasselmo, 2008c) focus on encoding associations between discrete sequential states (items or locations). However, recent data on grid cell firing in the entorhinal cortex (Barry et al., 2007, Hafting et al., 2005, Moser and Moser, 2008 and Sargolini et al., 2006) suggests a different approach (Hasselmo, 2008b) in which each individual state (place) is associated with an action (the velocity coded by speed-modulated head direction cells).
This model of the episodic encoding and retrieval of trajectories can use either of two main classes of grid cell models. One class of models generates grid cells based on interference patterns (Burgess, 2008 and Burgess et al., 2007). This model could use mechanisms of membrane potential oscillations shown in entorhinal neurons (Alonso and Llinas, 1989, Giocomo and Hasselmo, 2008a, Giocomo and Hasselmo, 2008b, Giocomo et al., 2007 and Hasselmo et al., 2007), or could use mechanisms of stable persistent spiking (Egorov et al., 2002, Fransén et al., 2006, Hasselmo, 2008a and Tahvildari et al., 2007). The other class of models uses attractor dynamics to generate grid cell activity (Fuhs and Touretzky, 2006 and McNaughton et al., 2006). The first type of model is used here, but either or both types of models could be used, because both models update grid cell position with a velocity signal from head direction cells. As shown here, a circuit mechanism using grid cells provides a substrate for encoding and retrieval of trajectories defined on continuous dimensions of space and time.
