Fan Cells in Layer 2 of the Lateral Entorhinal Cortex Are Critical for Episodic-like Memory

Curr Biol. 2020 Jan 6;30(1):169-175.e5. doi: 10.1016/j.cub.2019.11.027. Epub 2019 Dec 12.


Episodic memory requires different types of information to be bound together to generate representations of experiences. The lateral entorhinal cortex (LEC) and hippocampus are required for episodic-like memory in rodents [1, 2]. The LEC is critical for integrating spatial and contextual information about objects [2-6]. Further, LEC neurons encode objects in the environment and the locations where objects were previously experienced and generate representations of time during the encoding and retrieval of episodes [7-12]. However, it remains unclear how specific populations of cells within the LEC contribute to the integration of episodic memory components. Layer 2 (L2) of LEC manifests early pathology in Alzheimer's disease (AD) and related animal models [13-16]. Projections to the hippocampus from L2 of LEC arise from fan cells in a superficial sub-layer (L2a) that are immunoreactive for reelin and project to the dentate gyrus [17, 18]. Here, we establish an approach for selectively targeting fan cells using Sim1:Cre mice. Whereas complete lesions of the LEC were previously found to abolish associative recognition memory [2, 3], we report that, after selective suppression of synaptic output from fan cells, mice can discriminate novel object-context configurations but are impaired in recognition of novel object-place-context associations. Our results suggest that memory functions are segregated between distinct LEC networks.

Keywords: Alzheimer’s; associative memory; episodic memory; fan cells; hippocampus; lateral entorhinal cortex; medial entorhinal cortex; object recognition; recognition memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Entorhinal Cortex / physiology*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Male
  • Memory, Episodic*
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Recognition, Psychology
  • Reelin Protein
  • Serine Endopeptidases / metabolism


  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • Reln protein, mouse
  • Serine Endopeptidases