Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

Abstract

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

Disentangling the Role of the MEC and LEC in the Processing of Spatial and Non-Spatial Information: Contribution of Lesion Studies

“…Consistent with this finding, Kuruvilla and Ainge ( 2017 ) showed that the involvement of the LEC in object recognition depended on the number of objects located in the environment suggesting that the LEC is involved when the animal has to perform a complex task (four objects) but not a simpler task (two objects). These results are also coherent with a recent study from Ku et al ( 2017 ) that showed a greater involvement of the LEC as a function of the number of items to be processed (5 vs.10 odors) in an odor recognition task.…”

“…The notion that cognitive demand is an important factor that modulates the involvement of the MEC and LEC mainly arises from object exploration tasks. Interestingly, the importance of the LEC in high memory load conditions has been described in a recognition task involving odors (Ku et al, 2017 ) and in rat trace eyeblink conditioning (Morrissey et al, 2012 ). Whether task demand or task complexity is a relevant notion to account for a potential different involvement of the two sub-regions in navigation and between navigation and more spontaneous exploration tasks is an open question.…”

Opposing and Complementary Topographic Connectivity Gradients Revealed by Quantitative Analysis of Canonical and Noncanonical Hippocampal CA1 Inputs

“…This property of SUB networks could potentially explain the propensity for CA1 populations to exhibit highly similar spatial firing patterns under circumstances in which animals explore two environments sharing shape, alignment, and spatial distribution of boundary cues ( Skaggs and McNaughton, 1998 ; Spiers et al, 2015 ; Grieves et al, 2016 ). Notably, this phenomenon has direct impact in promoting learning of nonspatial associations ( Morris et al, 1990 ; Grieves et al, 2016 ) and is consistent with recent findings revealing a role for proximal SUB, proximal CA3, and LEC in memory for exposure to specific odors ( Nakamura et al, 2013 ; Ku et al, 2017 ). Finally, the organization of CA1 place-specific firing according to the reference frame of the observable environmental boundaries may be enhanced by SUB “boundary vector cells” that encode specific environmental borders ( Lever et al, 2009 ).…”

The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3

“…This might indicate that the LEC is the source of temporal information provided to distal CA1. Preliminary data from the Moser laboratory using population-level analyses of electrohysiological recordings partly support this hypothesis by reporting that LEC’s involvement within this frame depends on tasks’ demands, with free foraging tasks eliciting a stronger temporal representation in the LEC than continuous alternation/back-and-forth running tasks [ 69 ]; of note, such tasks’ demand dependency in the LEC were also reported in recent lesion and Arc imaging studies, albeit for the processing object and space information [ 70 , 71 ]. Our findings of a preferential involvement of distal CA1 in time processing depart from the standard model of episodic memory which, by extrapolation, predicts that temporal information would rather be processed by proximal CA1 because it mainly receives projections from the MEC, a part of the “where–when” pathway [ 2 , 4 ].…”