Recognition memory: Cellular evidence of a massive contribution of the LEC to familiarity and a lack of involvement of the hippocampal subfields CA1 and CA3

Abstract

A highly debated issue in memory research is whether familiarity is supported by the parahippocampal region, especially the lateral (LEC) and the perirhinal (PER) cortices, or whether it is supported by the same brain structure as recollection: the hippocampus. One reason for this is that conflicting results have emerged regarding the contribution of the hippocampus to familiarity. This might stem from the lack of dissociation between hippocampal subfields CA1 and CA3 as these areas are involved to a different extent in processes which are pertinent to familiarity. Another reason is that empirical evidence for a contribution of the LEC is still missing. Furthermore, it is unclear whether the superficial and the deep layers of the LEC would equally contribute to this process as these layers are differentially recruited during memory retrieval which partly relies on familiarity. To identify the specific contribution of the LEC, CA1, and CA3, we imaged with cellular resolution activity in the brain of rats performing a version of a standard human memory task adapted to rats that yields judgments based on familiarity. Using this translational approach, we report that in striking contrast to CA1 and CA3, the LEC is recruited for familiarity-judgments and that its contribution is comparable to that of the PER. These results show for the first time that the LEC, specifically its deep layers, contributes to familiarity and constitute the first cellular evidence that the hippocampus does not, thus establishing that familiarity does not share the same neural substrate as recollection.

Recognition memory: familiarity signals increase selectively in the lateral entorhinal cortex following hippocampal lesions

“…The fact that LEC is recruited during recognition memory based on familiarity in the present study supports the findings of the only study to date reporting a specific activation of LEC during familiarity judgments, albeit using different experimental conditions 17 . Altogether these results indicate, by extension, that familiarity-induced signals observed in humans in the rhinal cortices do truly involve LEC and not only PER.…”

“…This underlines the robustness of the findings and the fact that this result is independent of experimental conditions. Also, as mentioned previously, even though the role of PER in familiarity has been extensively studied in humans and rodents 12,13,15,16,14,17,18,7,53 , evidence for a specific involvement of LEC has been scarce in animals 17 and inexistent in humans. Hence, the extent to which the engagement of LEC and PER during judgments based on familiarity is comparable in healthy subjects or when hippocampal function is compromised was not known.…”

“…2A) 41 . Hippocampal ROIs (only in HIP intact rats) were defined based on HIP areas showing maximal Arc expression in the same task 17 .…”

“…single objects, odors etc…) mainly based on its strong anatomical ties with PER 7, 8 , while others have attributed this function to HIP in addition to its well-accepted role in the recollection of episodic events 9,10,11 . Plethora of studies have reported a specific involvement of PER in the familiarity process, especially during spontaneous object recognition memory in rodents and word recognition memory in humans 12,13,14,15,16,17,18,7,8 . In contrast, clear empirical evidence for a specific involvement of LEC in familiarity judgements is lacking in humans, essentially because human studies typically investigate BOLD signal in the anterior parahippocampal gyrus reflecting the activation of both PER and LEC.…”

“…8 Likewise, evidence for a role of the LEC in familiarity in animals is very scarce with, to date, only one study reporting a clear contribution of this area using a response deadline design yielding familiarity judgments. 17 This is a clear shortcoming as conflicting reports suggest that LEC and PER might not constitute a single functional entity. 19,20,21 Thus, the extent to which familiarity truly relies on LEC function remains unclear.…”