Abstract
Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses are located at the membranous neuronal protrusions called dendritic spines. The ability to change synaptic connections involves both alterations at the morphological level and changes in postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes the structural and functional plasticity of local synapses by its effect on glutamate receptor mobility and content. We used live imaging of cultured hippocampal neurons and quantitative morphological analysis to show that chemical long-term potentiation (cLTP) induces the permanent enlargement of a subset of small dendritic spines in an MMP-dependent manner. We also used a superresolution microscopy approach and found that spine expansion induced by cLTP was accompanied by MMP-dependent immobilization and synaptic accumulation as well as the clustering of GluA1-containing AMPA receptors. Altogether, our results reveal novel molecular and cellular mechanisms of synaptic plasticity.
Highlights
Dendritic spines are small membranous protrusions along neuronal dendrites
Niedringhaus et al (2012) have demonstrated an enhancement of matrix metalloproteinase (MMP)-dependent neuronal activity within in vitro networks of hippocampal neurons subjected to chemical long-term potentiation (cLTP) protocol
We confirmed that treatment with rolipram, forskolin, and picrotoxin produced lasting enhancement of network activity, reflected by increases in both spiking and bursting activity (Fig. S1)
Summary
Dendritic spines are small membranous protrusions along neuronal dendrites. The spines are the primary sites for excitatory synapses. The remarkable feature of excitatory synapses is their structural variability ranging from long, thin spines to short stubby- and mushroom-shaped spines. The cellular models of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), associate synaptic strength with either spine enlargement or spine shrinkage, respectively [1,2,3]. The structural rearrangement of preexisting spines and either the formation or loss of synapses accompany learning and memory processes [4,5]; for review, see [1,6]. Alterations in dendritic spine shape, size, and density are associated with a large number of brain disorders, indicating that dendritic spines may serve as a common substrate for various neuropsychiatric conditions, including epilepsy, autism spectrum disorder, schizophrenia, addiction, and Alzheimer’s disease [7,8,9,10,11,12,13,14]
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