Ultrastructural Abnormalities in CA1 Hippocampus Caused by Deletion of the Actin Regulator WAVE-1

Diána Hazai,Scott H Soderling,Bence Rácz,Jindong Ding,Richard J Weinberg,Róbert Szudoczki,Péter Sótonyi,Laurent Groc

doi:10.1371/journal.pone.0075248

Diána Hazai, Scott H Soderling + Show 6 more

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https://doi.org/10.1371/journal.pone.0075248

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Abstract

By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus.

Highlights

Most excitatory neurons in the mammalian forebrain have a long axon, and several shorter dendrites covered with spines
We conclude that while deletion of WAVE-1 slightly increased the number of terminals in CA1 stratum radiatum, it substantially reduced the fraction of terminals that make visible synapses with spines
Changes in synaptic efficacy are typically associated with morphological changes, in part because the biochemical cascades implicated in synaptic plasticity share common signaling pathways with the machinery controlling actin dynamics and reorganization [39]

Summary

Introduction

Most excitatory neurons in the mammalian forebrain have a long axon, and several shorter dendrites covered with spines. These dendritic spines are the primary target of glutamatergic axon terminals; modifications in spine shape and size are associated with multiple forms of long-term synaptic plasticity [1]. Actin is found in presynaptic axon terminals, where it can modulate the organization of the different pools of synaptic vesicles [6,7]. By creating a barrier between the reserve pool and the presynaptic active zone, Factin may lower release probability [8]; through interaction with synapsins, actin can facilitate transfer of vesicles from the reserve pool into the readily-releasable pool [9]. The actin cytoskeleton is important for both pre- and postsynaptic function

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