Discussion

The present observations on PRC, LEC and MEC neuronal firing patterns quite dramatically reject the notion that PRC and LEC neurons selectively encode object information whereas MEC neurons selectively encode spatial information. Given the direct and indirect connections between these areas (Suzuki & Amaral, 1994; Witter et al., 1989; Burwell & Amaral, 1998; Kerr et al., 2007), it should be expected that information processed in each of these areas is shared with the other. However, the extent to which individual PRC, LEC and MEC neurons, including even grid cells, border, and head direction cells, process both object and spatial

information equally is surprising. At the same time, population analyses strikingly dissociated PRC and LEC from MEC networks as prioritizing object and spatial information, respectively. These observations reinforce conclusions from recent studies that the full content and organization of representations in higher order brain areas is most clearly revealed in population analyses (Rigotti et al., 2013; Shamir, 2014).

Given the previous reports of striking coding of specific spatial dimensions (position, direction, borders) in MEC neurons, it was quite surprising that MEC

neurons of all subtypes (grid, border, head direction, other) strongly encoded object information and did so at least as well as PRC and LEC neurons. Also, given previous observations suggesting a lack of spatial coding by PRC and LEC neurons

(Hargreaves et al., 2005; Deshmukh et al., 2012), it was quite surprising that PRC and LEC neurons strongly encoded position and context, although not quite matching that seen in MEC. The most obvious difference in the present study and previous work is that both spatial and object dimensions were salient features of the task demands in this context-guided object-reward association paradigm. However, it is notable that both spatial context, which is important for task performance, and position within contexts, which is not required for task performance, were strongly encoded by PRC, LEC and MEC. Perhaps, once contextual spatial cues are relevant, both global and local spatial information become sufficiently salient to demand representation. This interpretation is consistent with other recent studies that have previously identified spatial coding in a minority of LEC cells (Deshmukh et al., 2011; Tsao et al., 2013). Both studies provided evidence of spatial “memory” fields at prior locations when objects were moved in or removed from the environment, while Deshmukh and colleagues also provided examples of activity similar to place field firing when objects were presented. In addition, studies on earlier stages of information processing prior to LEC and MEC, that is in the PRC and postrhinal cortex, have also reported mixed selectivity of neuronal activity in animals

performing memory tasks where objects and spatial choices are relevant (Furtak et al., 2012; Ahn et al., 2015). The present findings suggest that both LEC and MEC also

represent organizations of objects and events within spatial contexts (see also Knierim et al., 2013), and that even PRC exhibits a combination of object and spatial coding.

It was particularly striking that grid cells strongly encoded object

information, often differentiating objects sampled at the same location (See Figure 4). In contrast to the common view that grid cells are specialized for position

coding, results from the present study strongly suggest that grid cells possess strong object-coding properties that have been largely overlooked to this point. Future investigation of these properties could yield further insights about the organization of information in cortical structures of the hippocampal region and beyond, given the detailed understanding of grid cell function and organization (Moser & Moser, 2013; Moser et al., 2014; Witter et al., 2014).

The Representational Similarity Analysis employed here revealed that, within equivalent coding of specific dimensions by single PRC, LEC and MEC neurons, populations of neurons in all these areas developed distinct systematic organizations of those dimensions. Notably, both areas developed quite separate (anti-correlated) networks consistent with the opposite reward associations of objects in the two contexts. Other recent studies have shown that grid cell firing patterns in MEC are responsive to contextual differences (Marozzi et al., 2015) as well as a merging of spatial contexts (Carpenter et al., 2015). Furthermore, strong pattern separation of contextual representation was also observed in the

2014). Thus, contrary to other work suggesting that pattern separation occurs selectively within subregions of the hippocampus (Leutgeb et al., 2004; Lee et al., 2004; Bakker et al., 2008), here the entire hippocampal system responds to a strong demand for reducing interference between the opposite object associations in the two contexts by robust pattern separation.

Within the two context-based networks, PRC, LEC and MEC organize the object and spatial information quite differently. Within each context-based network, the closely interconnected PRC and LEC populations distinguish objects and then only within each object representation distinguish the positions where objects are sampled. Conversely, within each context-based network, MEC populations

distinguish the positions where object sampling occurs, and then only within each position representation distinguish the objects at those locations. Notably, the population representation within the MEC is very similar to that observed in the hippocampus (McKenzie et al., 2014), suggesting a prominent role of MEC in driving spatial organization in the hippocampus. Overall, this pattern of findings suggests we move from thinking about modality specific processing areas within the hippocampal system (Eichenbaum et al., 2007) to conceiving the hippocampal system as composed of interconnected areas each of which process all the information but differently organize the dimensions of information processing.