in principal, can respond to 50,000 odorant combinations (Fig. 3A; Jortner et al., 2007; Perez-Orive et al., 2002). Discriminating between two trajectories (assembly sequences) of hippocampal or prefrontal neurons by downstream readers, corresponding to two different choices, is a relatively simple task (Figure 4). On the other hand, segregating large numbers of trajectories, representing all episodes collected in one’s lifetime, requires complex mechanisms with many dedicated readers. Such system of readers with the ability to effectively orthogonalize upstream patterns is exemplified by the strong divergence of the entorhinal cortex-dentate granule cell connectivity and the sparse responses of granule cells (Jung and McNaughton, 1993; Leutgeb et al., 2007).19 On a larger scale, the entire neocortex can be conceived as a segregating orthogonalizing layer, with its reader mechanisms learning to classify and segregate overlapping hippocampal output patterns and lay them down as memories (McLelland et al., 1995) or translate them to plans and overt behavioral responses.
