Abstract
Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs), a family of extracellularly acting and Zn2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs) are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP) in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.
Highlights
Dendritic spines are small membranous protrusions that extend from neuronal dendrites
We demonstrate that chemically induced long-term potentiation (cLTP) induced by forskolin, rolipram and picrotoxin increases endogenous matrix metalloproteinases (MMPs)-9 activity at dendritic spines which regulate the formation of Spine head protrusions (SHPs) during cLTP in dissociated hippocampal cultures
The present study demonstrated that cLTP induced by forskolin, rolipram, and picrotoxin increased endogenous MMP9 activity and drove the formation of protrusions from dendritic spine heads in cultured neurons
Summary
Dendritic spines are small membranous protrusions that extend from neuronal dendrites. The majority of excitatory synapses in the mammalian brain are accommodated at the dendritic spines, representing the postsynaptic compartments of neuronal synapses. The spines exhibit considerable structural diversity and have been divided into distinct morphologic categories [1]. Their shapes include thin, filopodia-like protrusions (thin spines), short spines without a well-defined neck (stubby spines), and spines with a large bulbous head (mushroom spines). The morphology of dendritic spines is known to reflect their function. Alterations in spine morphology and turnover are thought to play a major role in neuronal plasticity, including learning processes [2,3]
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