Distinct spatial maps and multiple object codes in the lateral entorhinal cortex

Abstract

The lateral entorhinal cortex (LEC) is a major cortical input area to the hippocampus and it is crucial for associative object-place-context memories. An unresolved question is whether these associations are performed exclusively in the hippocampus or also upstream thereof. Anatomical evidence suggests that the LEC processes both object and spatial information. We here describe a gradient of spatial selectivity along the antero-posterior axis of the LEC. We demonstrate that the LEC generates distinct spatial maps for different contexts that are independent of object coding and vice versa, thus providing evidence for pure spatial and pure object codes upstream of the hippocampus. Whilst space and object coding occur by and large separately in the LEC, we identified neurons that encode for space and objects conjunctively. Together, these findings point to a scenario in which the LEC sustains both distinct space and object coding as well as associative space-object coding.

Ternary representation of contextual information along the CA1 transverse axis

“…For the novel-object task, while the role of PER in object-recognition memory is well- established, the contribution of the hippocampus and LEC to this process has been debated (Aggleton et al 2020). Our results suggest that the enhanced local response to the novel object in dCA1 (Figure 6) could be attributed to modified inputs from neurons in LEC and PER that are specific to object identity (Deshmukh et al 2011, Burke et al 2012, Deshmukh et al 2012, Huang et al 2023). Although further research is needed to determine whether PER input alone is sufficient for novel object representation in CA1, our findings underscore a potential role for dCA1 in object identity discrimination.…”

“…However, the regional variance in response to the novel object was primarily attributed to the subtle difference in activity change around the object (bins around the novel object: pCA1, 0.005 (−0.014–0.028), mCA1, 0.034 (0.021–0.046), dCA1, 0.070 (0.053–0.082), H = 61.612, P < 0.001, 120 bins; post hoc tests, all P ≤ 0.001), as ensemble activity changes outside the object region remained largely constant across CA1 subregions (bins outside the object region: pCA1, 0.035 (0.009–0.069), mCA1, 0.041 (0.023–0.064), dCA1, 0.044 (0.012–0.078), H = 5.689, P = 0.058, 1,080 bins; Figures 6G and S7M). To conclude, place cells located more distally along the CA1 transverse axis displayed greater firing rate redistribution around the novel object, likely due to preferential inputs from object-identity cells from LEC and PER (Deshmukh et al 2011, Burke et al 2012, Deshmukh et al 2012, Huang et al 2023).…”

“…We uncovered three distinct patterns of cue representation along the proximo-distal axis in CA1 that may affect the overall output of hippocampal function: a gradient of decreasing spatial information processing, an increase in the representation of local object features, and most intriguingly, a reverse J- shaped response to non-spatial environmental changes (Figure S8). These patterns in population response are largely attributed to the distinct nature of contextual cues, and their association with selective inputs from particular neuron populations, predominately locating in the entorhinal cortex (Deshmukh et al 2011, Tsao et al 2013, Wang et al 2018, Tukker et al 2022, Huang et al 2023).…”

“…The elevated rate redistribution in both pCA1 and dCA1 may suggest contributions from both MEC and LEC to hippocampal rate coding. Certain LEC neurons are known to remap in response to contextual changes in the environment, and disrupting LEC function through lesions has been shown to partially impair rate coding in CA3 (Lu et al 2013, Huang et al 2023). This supports the hypothesis that LEC provides modulated non-spatial inputs critical for hippocampal rate remapping (Renno-Costa et al 2010).…”

“…The medial division of the entorhinal cortex (MEC) contains several specialized cell types, including grid cells (Hafting et al 2005), aperiodic spatial cells (Fyhn et al 2004), head direction cells (Sargolini et al 2006), border cells (Solstad et al 2008), and speed cells (Kropff et al 2015), which together form a dynamic representation of the animal’s location in space (Long et al 2022, Tukker et al 2022). In contrast, the lateral division of the entorhinal cortex (LEC) exhibits minimal spatial selectivity in open fields (Hargreaves et al 2005, Huang et al 2023). Most neurons in LEC represent non-spatial features of the animal’s ongoing experience, such as object (Deshmukh et al 2011, Tsao et al 2013), odor (Igarashi et al 2014, Leitner et al 2016), time (Tsao et al 2018), and animal’s egocentric position relative to landmarks (Wang et al 2018), supplying the hippocampus with a temporal progression of events (Sugar et al 2019).…”