In addition the firing patterns of time cells are also dependent on location and other behavioral variables, just as the spatial activity of place cells is also

dependent on nonspatial variables. GSK1210151A research buy We believe the term “time cell” is appropriate to describe the temporal-coding properties of these hippocampal neurons, just as the term “place cell” is appropriate to describe their spatial firing patterns. Previous work on hippocampal neuronal activity in rats performing T-maze alternation tasks has shown that hippocampal neuronal ensembles similarly disambiguate overlapping spatial routes (Frank et al., 2000 and Wood et al., 2000; reviewed in Shapiro et al., 2006). In an extension of those studies, Pastalkova et al.

(2008) revealed the existence of hippocampal neurons that fire at specific moments as rats walk on a running wheel between trials, and some of these cells distinguished subsequent left and right turn trials. The present observations indicate that hippocampal neurons also encode specific times between nonspatial events and disambiguate nonspatial sequences, extending the observation of time cells to filling gaps within a specific nonspatial memory. Several models have proposed that hippocampal neuronal activity supports the temporal organization of memories by the encoding and retrieval of specific events that compose a sequence, by distinct representations of common events in overlapping sequences, PD-1/PD-L1 inhibitor 2 and by bridging gaps between discontiguous until events (Rawlins, 1985, Levy, 1989, Wallenstein et al., 1998, Jensen

and Lisman, 2005 and Howard et al., 2005). In support of these models, experimental studies on both humans (Gelbard-Sagiv et al., 2008 and Paz et al., 2010) and animals (Louie and Wilson, 2001, Foster and Wilson, 2006, Karlsson and Frank, 2009 and Davidson et al., 2009) have shown that hippocampal neuronal ensembles “replay” specific event representations following learning. Temporal order in episodic memories is also supported by a gradually changing representation of the temporal context of successive events (Manns et al., 2007). Manns et al. (2007) did not determine how the temporal organization of neural activity bridges the gap between discontiguous events and, because the sequences were trial unique, their study did not show how specific sequences are encoded within the changing temporal context signal. The current findings are entirely compatible with those earlier results, and now show that distinct repeated experiences are represented by sequential neuronal firing patterns that reflect both the changing temporal context and a specific series of events.