Parahippocampal latrophilin-2 (ADGRL2) expression controls topographical presubiculum to entorhinal cortex circuit connectivity.

Jordan D. Donohue,Anthony J. Wong,Haneal Pae,Alexander J. King,Garret R. Anderson,Elizabeth D. Liu,Ryan F. Amidon,Lisette Saab,Moyinoluwa T. Ajayi,Thomas R. Murphy

doi:10.1016/j.celrep.2021.110031

Jordan D. Donohue, Anthony J. Wong + Show 8 more

Open Access

https://doi.org/10.1016/j.celrep.2021.110031

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Journal: Cell Reports	Publication Date: Nov 1, 2021
Citations: 9	License type: cc-by

Affiliation: University of California, Riverside

Abstract

Brain circuits are comprised of distinct interconnected neurons that are assembled by synaptic recognition molecules presented by defined pre- and post-synaptic neurons. This cell-cell recognition process is mediated by varying cellular adhesion molecules, including the latrophilin family of adhesion G-protein-coupled receptors. Focusing on parahippocampal circuitry, we find that latrophilin-2 (Lphn2; gene symbol ADGRL2) is specifically enriched in interconnected subregions of the medial entorhinal cortex (MEC), presubiculum (PrS), and parasubiculum (PaS). Retrograde viral tracing from the Lphn2-enriched region of the MEC reveals unique topographical patterning of inputs arising from the PrS and PaS that mirrors Lphn2 expression. Using a Lphn2 conditional knockout mouse model, we find that deletion of MEC Lphn2 expression selectively impairs retrograde viral labeling of inputs arising from the ipsilateral PrS. Combined with analysis of Lphn2 expression within the MEC, this study reveals Lphn2 to be selectively expressed by defined cell types and essential for MEC-PrS circuit connectivity.

Highlights

Episodic learning and memory encoding in the brain involves interplay between the hippocampus and entorhinal cortex (EC) to provide detailed spatial and temporal information
Superficial layers of the EC send their projections to the hippocampus, with layer II stellate cells projecting to the dentate gyrus (DG) and layer III pyramidal cells projecting to the stratum lacunosum moleculare region (SLM) of the CA1
Given the marked cell type-specific expression and synapsespecific function of Lphn2 observed in the hippocampus, in this study we investigate the role of Lphn2 in the greater hippocampal-entorhinal circuit

Summary

Introduction

Episodic learning and memory encoding in the brain involves interplay between the hippocampus and entorhinal cortex (EC) to provide detailed spatial and temporal information. There are classically defined cellular and pathway-specific circuits that exist between the parahippocampal EC and hippocampal formation that allow for bidirectional communication between the two structures (Basu and Siegelbaum, 2015; Nilssen et al, 2019). In addition to cellular layer-specific synaptic communication, spatial-topographical circuit patterning is widely observed throughout the hippocampal-entorhinal circuit. The MEC receives input from the PrS, PaS, retrosplenial cortex, and postrhinal cortex, all regions implicated for spatial and episodic memory processing (Boccara et al, 2010; Witter and Moser, 2006; Witter et al, 2017). The LEC, in contrast, receives inputs from the perirhinal cortex and sensory areas and is thought to be involved in attention and multi-sensory association processing (Basu and Siegelbaum, 2015; Witter et al, 2017)

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