Deletion of the NMDA receptor GluN2A subunit significantly decreases dendritic growth in maturing dentate granule neurons.

Timal S Kannangara,Lee Thompson,Brian R Christie,Andrea Ratzlaff,Joana Gil-Mohapel,Crystal A Bostrom,Robyn M Cater,Laurent Groc

doi:10.1371/journal.pone.0103155

Timal S Kannangara, Lee Thompson + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0103155

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Journal: PloS one	Publication Date: Aug 1, 2014
Citations: 100	License type: CC BY 4.0

Affiliation: University of Victoria, University of British Columbia

Abstract

It is known that NMDA receptors can modulate adult hippocampal neurogenesis, but the contribution of specific regulatory GluN2 subunits has been difficult to determine. Here we demonstrate that mice lacking GluN2A (formerly NR2A) do not show altered cell proliferation or neuronal differentiation, but present significant changes in neuronal morphology in dentate granule cells. Specifically, GluN2A deletion significantly decreased total dendritic length and dendritic complexity in DG neurons located in the inner granular zone. Furthermore, the absence of GluN2A also resulted in a localized increase in spine density in the middle molecular layer, a region innervated by the medial perforant path. Interestingly, alterations in dendritic morphology and spine density were never seen in dentate granule cells located in the outer granular zone, a region that has been hypothesized to contain older, more mature, neurons. These results indicate that although the GluN2A subunit is not critical for the cell proliferation and differentiation stages of the neurogenic process, it does appear to play a role in establishing synaptic and dendritic morphology in maturing dentate granule cells localized in the inner granular zone.

Highlights

The generation of new neurons in the dentate gyrus (DG) of the hippocampus has been shown to persist throughout adulthood in many species [1,2,3], including humans [4]
The current results indicate that the GluN2A subunit of the NMDA receptor plays an important role in shaping the morphological characteristics of dentate granule cells (DGCs) in the inner granular zone (IGZ)
Deletion of the GluN2A subunit did not significantly alter adult hippocampal neurogenesis Interestingly, the morphological effects of GluN2A deletion were restricted to a subpopulation of DGCs located within the IGZ

Summary

Introduction

The generation of new neurons in the dentate gyrus (DG) of the hippocampus has been shown to persist throughout adulthood in many species [1,2,3], including humans [4]. Immature neurons proceed to sprout one or two primary dendrites that extend into the molecular layer, before maturing into neurons that are functionally and structurally indistinguishable from older neurons [8,9,10] This process of structural plasticity, formally referred to as adult neurogenesis, is tightly regulated, and can be modulated by synaptic activity [11]. These deficits were restricted to a subpopulation of DGCs typically characterized by the presence of a single apical dendrite and localized within the inner granular zone (IGZ) of the DG These results suggest that GluN2A-containing NMDA receptors play an important role during neuronal morphological maturation in the adult DG

Experimental Procedures

Results

Discussion

Role of the GluN2A subunit during adult hippocampal neurogenesis

Role of the GluN2A subunit in the dendritic morphology of DGCs