Medial Entorhinal Cortex Lesions Only Partially Disrupt Hippocampal Place Cells and Hippocampus-Dependent Place Memory

Abstract

SUMMARY Entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired at acquiring the watermaze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, MEC is not necessary for all types of spatial coding, nor for all types of hippocampus-dependent memory, but is necessary for the normal acquisition of place memory.

Cognitive Deficits in Calsyntenin-2-deficient Mice Associated with Reduced GABAergic Transmission

“…In another spatial task, displaced object recognition, Clstn2 -/-mice performed equally well as WT littermates, which is intriguing but explainable as several studies have shown a double dissociation between performance in the Morris water maze and displaced object recognition. While lateral entorhinal cortex lesions impair performance in the displaced object recognition task but not in the Morris water maze (Van Cauter et al, 2013), medial entorhinal cortex lesions impair performance in the Morris water maze but can spare behavior in the displaced object recognition task ( (Hales et al, 2014) but see (Van Cauter et al, 2013)). The © 2015 Macmillan Publishers Limited.…”

Spatial representation in the hippocampal formation: a history

“…Place fields have been reported to persist when the spatially periodic firing pattern of MEC grid cells is compromised by inactivation of septal inputs 181,182 , and in young animals, place cells acquire stable firing fields before sharp periodic firing patterns emerge in grid cells 183,184 . Inactivation or damage of the MEC is not sufficient to disrupt place cell firing in the hippocampus 128,131,132,185 . However, neither of these observations rules out grid cells as a key determinant of spatially selective firing in the hippocampus.…”

“…The fact that this effect occurs predominantly in CA1, which lacks the potential stabilizing effects of reciprocal excitatory connections present in CA3, tends to support such a view 127 . A second possible challenge is the fact that place fields can be expressed in CA1 under conditions in which the medial entorhinal cortex (MEC) is completely lesioned 128 . This suggests that localized firing may itself be generated from alternative inputs, such as from weakly spatially modulated neurons in the lateral entorhinal cortex (LEC) 129 , which may provide hippocampal cells with path-integrationindependent sensory inputs necessary for efficient rate coding 130 .…”

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory

“…Suthana et al (2012) showed improvements in navigation performance following acute stimulation of the entorhinal cortex, with their specific measure being the accuracy with which patients navigated to a goal location store (termed excess path length, i.e., Newman et al, 2007). Because navigation is often associated with integrity of the hippocampus (i.e., Astur, Taylor, Mamelak, Philpott, & Sutherland, 2002;Kolarik et al 2016;Morris & Garrud, 1982) and not of the entorhinal cortex (e.g., Hales et al, 2014), the authors attributed the effects of stimulation to entorhinal cortex as occurring because it resulted in more endogenous, regularized input into the hippocampus than direct stimulation of the hippocampus (Suthana et al, 2012). In support of this argument, direct stimulation of the hippocampus had no effect on navigation yet stimulation of entorhinal cortex did reset on-going low frequency oscillations in the hippocampus.…”