Abstract

Reelin is an extracellular matrix protein expressed in several interneuron subtypes in the hippocampus and dentate gyrus. Neuronal nitric oxide synthase (nNOS) is also expressed by interneurons in these areas. We investigated whether reelin and nNOS are co-localized in the same population of hippocampal interneurons, and whether this colocalization is altered in the heterozygous reeler mouse. We found colocalization of nNOS in reelin-positive cells in the CA1 stratum radiatum and lacunosum moleculare, the CA3 stratum radiatum, and the dentate gyrus subgranular zone, molecular layer, and hilus. In heterozygous reeler mice, the colocalization of nNOS in reelin-positive cells was significantly decreased only in the subgranular zone and molecular layer. The coexpression of reelin and nNOS in several hippocampal regions suggests that reelin and nNOS may work synergistically to promote glutamatergic function, and the loss of this coexpression in heterozygous reeler mice may underlie some of the behavioral deficits observed in these animals.

Highlights

  • Reelin is a large extracellular matrix protein that plays an important role in regulating neural migration and synaptogenesis during development

  • The results of this study provide the first data showing that a subset of reelin-positive cells throughout the hippocampus and dentate gyrus express Neuronal nitric oxide synthase (nNOS)

  • They revealed that this colocalization of reelin and nNOS is substantially decreased in heterozygous reeler mice

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Summary

Introduction

Reelin is a large extracellular matrix protein that plays an important role in regulating neural migration and synaptogenesis during development It is a key component of synaptic plasticity in the adult brain (see [1, 2], as recent reviews). Reelin influences neural plasticity primarily through activation of VLDLR and ApoER2 receptors (for a review, see [2]), but it increases translation of selective mRNAs in dendritic spines by binding to integrins located in the plasma membrane. One example of this is the recent observation that reelin can increase the translation of activity-related cytoskeletal protein (Arc) thereby influencing spine maturation and stability [9]. Reelin induces the clustering of its receptor [15], and increases the number of intramembrane particles (i.e., transmembrane proteins) in synaptosomal membranes [16]

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