Conflicts between Local and Global Spatial Frameworks Dissociate Neural Representations of the Lateral and Medial Entorhinal Cortex

Abstract

Manipulation of spatial reference frames is a common experimental tool to investigate the nature of hippocampal information coding and to investigate high-order processes, such as cognitive coordination. However, it is unknown how the hippocampus afferents represent the local and global reference frames of an environment. To address these issues, single units were recorded in freely moving rats with multi-tetrode arrays targeting the superficial layers of the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), the two primary cortical inputs to the hippocampus. Rats ran clockwise laps around a circular track partitioned into quadrants covered by different textures (the local reference frame). The track was centered in a circular environment with distinct landmarks on the walls (the global reference frame). Here we demonstrate a novel dissociation between MEC and LEC in that the global frame controlled the MEC representation and the local frame controlled the LEC representation when the reference frames were rotated in equal, but opposite, directions. Consideration of the functional anatomy of the hippocampal circuit and popular models of attractor dynamics in CA3 suggests a mechanistic explanation of previous data showing a dissociation between the CA3 and CA1 regions in their responses to this local–global conflict. Furthermore, these results are consistent with a model of the LEC providing the hippocampus with the external sensory content of an experience and the MEC providing the spatial context, which combine to form conjunctive codes in the hippocampus that form the basis of episodic memory.

Spatial and Nonspatial Representations in the Lateral Entorhinal Cortex

“…The hippocampal spatial representation is likely to be richer under these circumstances, given the fact that both landmark-derived spatial representation from LEC and path integration-derived spatial representation from MEC converge in the hippocampus in the presence of objects. The weak spatial tuning seen in LEC on the circular track (Yoganarasimha et al 2011) rotates with the track when the track and the distal cues are rotated in opposite directions (Neunuebel et al 2013). Consistent with the proposed role of LEC in sensory-derived information processing, this observation might indicate a rudimentary spatial representation derived from local textures and odors on the track.…”

“…MEC neurons also showed significantly higher correlations in their spatial firing patterns between the first and second halves of the session than the LEC neurons. Taken together, the Hargreaves et al (2005) and Yoganarasimha et al (2011) studies show that in a variety of simple and complex environments commonly used for studying spatial information processing in the hippocampus, MEC is the reliable source of spatial information to the hippocampus while LEC is not (but see Neunuebel et al 2013). Thus, the "where" component of the proposed "what/where" dichotomy in LEC and MEC was confirmed to be encoded in MEC but not in LEC under these conditions.…”

Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local–global reference frames

“…A recent study by Neunuebel et al [50] provides strong evidence for the local-global distinction between the LEC and MEC. Superficial MEC and LEC neurons were recorded as rats ran on a circular track with a set of salient local cues on the surface and a set of global landmarks on curtains at the perimeter of the recording environment.…”

“…Other cells fire like place cells in locations where the animal never experienced an object, but apparently only when individual objects are present in the environment [35]. Textures on the surface of a track or salient landmarks outside the apparatus are unable to support spatial firing [20] (although a weak spatial signal can be detected when local and global cues are placed in conflict, as described above [50]). Because LEC cells with spatial properties are rare and few studies of LEC have been performed in freely moving animals, we know very little about the properties of these cells and the cues that drive their firing.…”

Beyond the bolus: transgenic tools for investigating the neurophysiology of learning and memory

“…However, recent research indicates that eliminating the spatial firing pattern of grid cells by pharmacologically inactivating the medial septum has little effect on the maintenance and formation of place fields in familiar and novel environments, respectively (Koenig et al 2011;Brandon et al 2014). These and other recent empirical findings (Mizuseki et al 2009;Langston et al 2010;Wills et al 2010;Barry et al 2012;Neunuebel et al 2013;Neunuebel and Knierim 2014) challenge the idea of a simple grid to place cell transformation. Alternative network models developed prior to the discovery of grid cells suggest that the network exhibits place selective activity as a consequence of stable attractor states (Samsonovich and McNaughton 1997;Tsodyks 1999).…”