The role of the medial entorhinal cortex in spatial and temporal coding

Schlesiger, Magdalene I. (2016): The role of the medial entorhinal cortex in spatial and temporal coding. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)

Abstract

The hippocampus (HIPP) is the core of a memory system crucial for the formation of new episodic (unique event) memories in humans and episodic-like memories (for what, where and when) in rodents. Its prevalent role in the formation of memories is thought to rely on a variety of specialized neural network computations: It is for example believed that hippocampal networks associate information about different aspects of an experience (such as a particular event and the place at which the event occurred) into a coherent memory trace. In order to prevent interference between memories that are similar (such as two different experiences within the same place) each memory is assigned a neural code that is highly distinct from those for previously acquired memories. Finally, hippocampal networks are thought to fuse memories for individual fragments of an experience into a temporally structured sequence which represent an episode. Information about different aspects of an experience reaches the HIPP via the entorhinal cortex (EC), which is its major cortical input structure. Electrophysiological single-unit recordings in behaving rodents revealed that in particular the medial division of the EC (MEC) contains a variety of cell types that are specialized in the representation of spatial and self-motion information. It is therefore believed that input from the MEC supports the spatial component of memory processing in the HIPP. Here, we tested the long-standing hypothesis that hippocampal spatial coding relies on input from the MEC. This was achieved by performing extensive, bilateral excitotoxic lesions of the MEC and placing electrode arrays into the CA1 pyramidal cell layer of the HIPP. Hippocampal neural computations were assessed by recording extracellular action potentials (APs) from individual neurons as rats explored open field environments. The firing patterns of hippocampal neurons are known to correlate with the rat’s behavior, in that each cell fires APs at restricted proportions of the environment, forming spatial receptive fields (so-called place fields). The spatial precision and organization of those place fields was examined in control and MEC-lesioned rats. We found that hippocampal neurons retained their spatial selectivity after MEC lesions, even though the precision and stability of the hippocampal spatial code were reduced. The ability to form distinct spatial representation for different environments was entirely intact in MEC-lesioned rats. Contrary to most contemporary theories of hippocampo-entorhinal function, our findings suggest that the MEC is not the only determinant of hippocampal spatial computations and that sources lacking sophisticated spatial firing, such as the lateral division of the entorhinal cortex (LEC) and local hippocampal network computations are sufficient to support this function. Following the finding that spatial firing was partly preserved in MEC-lesioned rats, we tested whether the MEC is necessary for the temporal organization of spike timing within the place field. Hippocampal place cells that are activated along the rat’s trajectory through space are thought to be linked into synaptically connected neuronal sequences via a mechanisms referred to as hippocampal theta phase precession (hTPP). Theta phase precession reflects the temporal distribution of APs within each place field with reference to the local field potential (LFP) oscillation at theta frequency (4 to 10 Hz). We found that hTPP was strongly disrupted in MEC-lesioned rats, demonstrating that the MEC is necessary for the temporal organization of hippocampal spatial firing. Cognitive functions that rely on sequentially activated place cells are thus likely to rely on the MEC. In summary, the presented data demonstrate that the contribution of the MEC to hippocampal spatial coding is less predominant than postulated by contemporary theories of hippocampo-entorhinal function. In addition, the findings suggest that the MEC, which is widely considered a spatial processing center of the brain, supports memory through the temporal organization of hippocampal spatial firing.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Medial entorhinal cortex, grid cells, spatial memory, place cells
• Fakultäten: Graduate School of Systemic Neurosciences (GSN)
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 5. Dezember 2016
• 1. Bericht­erstatter:in: Leibold, Christian