The HSPG Glypican Regulates Experience-Dependent Synaptic and Behavioral Plasticity by Modulating the Non-Canonical BMP Pathway

Keisuke Kamimura,Aiko Odajima,Yuko Ikegawa,Chikako Maru,Nobuaki Maeda

doi:10.1016/j.celrep.2019.08.032

Keisuke Kamimura, Aiko Odajima + Show 3 more

Open Access

https://doi.org/10.1016/j.celrep.2019.08.032

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Abstract

Under food deprivation conditions, Drosophila larvae exhibit increases in locomotor speed and synaptic bouton numbers at neuromuscular junctions (NMJs). Octopamine, the invertebrate counterpart of noradrenaline, plays critical roles in this process; however, the underlying mechanisms remain unclear. We show here that a glypican (Dlp) negatively regulates type I synaptic bouton formation, postsynaptic expression of GluRIIA, and larval locomotor speed. Starvation-induced octopaminergic signaling decreases Dlp expression, leading to increases in synapse formation and locomotion. Dlp is expressed by postsynaptic muscle cells and suppresses the non-canonical BMP pathway, which is composed of the presynaptic BMP receptor Wit and postsynaptic GluRIIA-containing ionotropic glutamate receptor. We find that during starvation, decreases in Dlp increase non-canonical BMP signaling, leading to increases in GluRIIA expression, type I bouton number, and locomotor speed. Our results demonstrate that octopamine controls starvation-induced neural plasticity by regulating Dlp and provides insights into how proteoglycans can influence behavioral and synaptic plasticity.

Highlights

Neural plasticity is the ability of the nervous system to reorganize and modulate neural connections in response to internal and external stimuli and serves as the basis for learning and memory (Oberman and Pascual-Leone, 2013)
At type I synaptic boutons, postsynaptic responses to glutamate are mediated by tetrameric ionotropic glutamate receptors, which are homologous to mammalian a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors (Han et al, 2015)
We revealed that Dlp negatively regulated type I bouton growth and larval locomotor activity and suppressed non-canonical BMP signaling composed of the presynaptic BMP type II receptor Wit and postsynaptic GluRIIA subunit-containing ionotropic glutamate receptors (iGluRs) (Sulkowski et al, 2014, 2016)

Summary

Introduction

Neural plasticity is the ability of the nervous system to reorganize and modulate neural connections in response to internal and external stimuli and serves as the basis for learning and memory (Oberman and Pascual-Leone, 2013). It is important to note that higher vertebrates and invertebrates such as the fruit fly Drosophila melanogaster exhibit experience-dependent plasticity (Sigrist et al, 2003; Budnik and Ruiz-Canada, 2006; Schuster, 2006). Drosophila has long been used to study the effects of genetic mutations on synapse formation and behavior and serves as a simple model organism for the study of experience-dependent neural plasticity. Type I synapses exhibit structural similarities to the excitatory synapses of the mammalian brain with well-developed postsynaptic scaffolds that resemble mammalian postsynaptic densities (Budnik and Ruiz-Canada, 2006). Drosophila larval type I synapses have been regarded as a genetically tractable model for mammalian brain excitatory synapses

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