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

Brianna Vandrey; Derek L.F. Garden; Veronika Ambrozova; Christina McClure; Matthew F. Nolan; James A. Ainge

doi:10.1016/j.cub.2019.11.027

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

Brianna Vandrey, Derek L.F. Garden, Veronika Ambrozova, Christina McClure, Matthew F. Nolan^* (Corresponding Author), James A. Ainge^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

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, 3, 4, 5, 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, 8, 9, 10, 11, 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, 14, 15, 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.

Original language	English
Pages (from-to)	169-175.e5
Number of pages	12
Journal	Current Biology
Volume	30
Issue number	1
Early online date	12 Dec 2019
DOIs	https://doi.org/10.1016/j.cub.2019.11.027
Publication status	Published - 6 Jan 2020
Externally published	Yes

Bibliographical note

Funding Information:

This work was supported by a Carnegie Trust Collaborative Research Grant to J.A. and M.F.N. a Henry Dryerre scholarship from the Royal Society of Edinburgh to B.V. and grants from Wellcome Trust (200855/Z/16/Z) and BBSRC (BB/M025454/1) to M.F.N. Conceptualization and Methodology, B.V. M.F.N. and J.A.A.; Investigation, B.V. D.L.F.G. and V.A.; Resources, C.M.; Writing ? Original Draft, B.V.; Writing ? Review & Editing, B.V. M.F.N. and J.A.A.; Supervision, M.F.N. and J.A.A.; Funding Acquisition, B.V. M.F.N. and J.A.A. The authors declare no competing interests.

Data Availability Statement

Original data for the behavior experiments in the paper (Figures 3C, 4B, 4C, S3, and S4) is available at the University of Edinburgh Datashare Repository (https://doi.org/10.7488/ds/2629).

Keywords

recognition memory
associative memory
hippocampus
Alzheimer's
medial entorhinal cortex
object recognition
fan cells
lateral entorhinal cortex
episodic memory

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Cite this

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

abstract = "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, 3, 4, 5, 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, 8, 9, 10, 11, 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{\textquoteright}s disease (AD) and related animal models [13, 14, 15, 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.",

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AU - McClure, Christina

AU - Nolan, Matthew F.

AU - Ainge, James A.

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N2 - 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, 3, 4, 5, 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, 8, 9, 10, 11, 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, 14, 15, 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.

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

Abstract

Bibliographical note

Data Availability Statement

Keywords

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