Opposing Morphogenetic Defects on Dendrites and Mossy Fibers of Dentate Granular Neurons in CRMP3-Deficient Mice.

Tam Quach,Nathalie Auvergnon,Rajesh Khanna,Papachan Kolattukudy,Marie-Françoise Belin,Anne-Marie Duchemin,Jérome Honnorat

doi:10.3390/brainsci8110196

Abstract

Collapsin response mediator proteins (CRMPs) are highly expressed in the brain during early postnatal development and continue to be present in specific regions into adulthood, especially in areas with extensive neuronal plasticity including the hippocampus. They are found in the axons and dendrites of neurons wherein they contribute to specific signaling mechanisms involved in the regulation of axonal and dendritic development/maintenance. We previously identified CRMP3’s role on the morphology of hippocampal CA1 pyramidal dendrites and hippocampus-dependent functions. Our focus here was to further analyze its role in the dentate gyrus where it is highly expressed during development and in adults. On the basis of our new findings, it appears that CRMP3 has critical roles both in axonal and dendritic morphogenesis of dentate granular neurons. In CRMP3-deficient mice, the dendrites become dystrophic while the infrapyramidal bundle of the mossy fiber shows aberrant extension into the stratum oriens of CA3. This axonal misguided projection of granular neurons suggests that the mossy fiber-CA3 synaptic transmission, important for the evoked propagation of the activity of the hippocampal trisynaptic circuitry, may be altered, whereas the dystrophic dendrites may impair the dynamic interactions with the entorhinal cortex, both expected to affect hippocampal function.

Highlights

The dentate gyrus (DG) is involved in the pathophysiology of epilepsy, acute and chronic stress, mood disorders, and age-related cognitive dysfunction [1,2,3,4]
A dominant β-galactosidase distribution was found in hippocampus and especially in granule neurons (GN) (Figure 1A, Appendix A) of Collapsin Response Mediator Protein 3 (CRMP3)−/− mice, confirming previous CRMP3 in situ hybridization data of the high distribution of CRPM3 in DG [21]
No gross DG anatomical abnormalities in adult CRMP3−/− mice were observed by light microscopy of cresyl violet- (Figure 1B,C) or DAPI- (Figure 1D,E) stained sections of the hippocampus, there was a poor alignment and tortuous appearance of the dendritic arbor in DG from CRMP3−/− mice (Figure 1F) visualized by MAP2 staining

Summary

Introduction

The dentate gyrus (DG) is involved in the pathophysiology of epilepsy, acute and chronic stress, mood disorders, and age-related cognitive dysfunction [1,2,3,4]. (1) the molecular layer/stratum moleculare contains the dendrites of granule neurons (GN) as well as fibers of the perforant path that originate from the entorhinal cortex, and various inter-neurons types; Brain Sci. 2018, 8, 196; doi:10.3390/brainsci8110196 www.mdpi.com/journal/brainsci. (2) the granular layer/stratum granulosum consists of packed GNs. Their unmyelinated axons, the mossy fibers (MF), have two bundles: a short infrapyramidal bundle (IPB) and a long main bundle (MB), referred to as stratum lucidum, which invades the hilar region, passing along the apical dendrites of CA3 pyramidal cells and collaterizing with basket cells before entering the CA3 field and contacting the proximal parts of the basal dendrites; (3) the hilar layer/hilus contains polymorphic cells [6]. Several factors contributing to the development and maturation of dendrites and axons of DG have been identified [10,11,12], the understanding of the mechanisms regulating this highly organized neuroanatomical structure remains incomplete

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