Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation

• Published in: PloS one Vol. 8; no. 5; p. e63314
• Main Authors: Szepesi, Zsuzsanna, Bijata, Monika, Ruszczycki, Blazej, Kaczmarek, Leszek, Wlodarczyk, Jakub
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.05.2013; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Cells, Cultured; Dendrites; Dendritic spines; Dendritic Spines - metabolism; Dendritic structure; Extracellular matrix; Filopodia; Gelatinase B; Hippocampus; Long-term potentiation; Long-Term Potentiation - physiology; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Medicine; Memory; Microtubules - metabolism; Morphology; Neurobiology; Neurons; Neurosciences; Potentiation; Propionic acid; Pseudopodia; Rats; Rats, Wistar; Receptors; Receptors, AMPA - metabolism; Rodents; Spine; Synapses; Zinc; Zinc compounds; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063314

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 Zn(2+)-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.