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In vivo roles for matrix metalloproteinase-9 in mature hippocampal synaptic physiology and plasticity.
- Source :
-
Journal of neurophysiology [J Neurophysiol] 2007 Jul; Vol. 98 (1), pp. 334-44. Date of Electronic Publication: 2007 May 09. - Publication Year :
- 2007
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Abstract
- Extracellular proteolysis is an important regulatory nexus for coordinating synaptic functional and structural plasticity, but the identity of such proteases is incompletely understood. Matrix metalloproteinases (MMPs) have well-known, mostly deleterious roles in remodeling after injury or stroke, but their role in nonpathological synaptic plasticity and function in intact adult brains has not been extensively investigated. Here we address the role of MMP-9 in hippocampal synaptic plasticity using both gain- and loss-of-function approaches in urethane-anesthetized adult rats. Acute blockade of MMP-9 proteolytic activity with inhibitors or neutralizing antibodies impairs maintenance, but not induction, of long-term potentiation (LTP) at synapses formed between Schaffer-collaterals and area CA1 dendrites. LTP is associated with significant increases in levels of MMP-9 and proteolytic activity within the potentiated neuropil. By introducing a novel application of gelatin-substrate zymography in vivo, we find that LTP is associated with significantly elevated numbers of gelatinolytic puncta in the potentiated neuropil that codistribute with immunolabeling for MMP-9 and for markers of synapses and dendrites. Such increases in proteolytic activity require NMDA receptor activation. Exposing intact area CA1 neurons to recombinant-active MMP-9 induces a slow synaptic potentiation that mutually occludes, and is occluded by, tetanically evoked potentiation. Taken together, our data reveal novel roles for MMP-mediated proteolysis in regulating nonpathological synaptic function and plasticity in mature hippocampus.
- Subjects :
- Animals
Dose-Response Relationship, Radiation
Electric Stimulation
Enzyme Inhibitors pharmacology
Glial Fibrillary Acidic Protein metabolism
Immunoglobulin G pharmacology
Long-Term Potentiation drug effects
Long-Term Potentiation radiation effects
Male
Matrix Metalloproteinase 9 immunology
Matrix Metalloproteinase Inhibitors
Microtubule-Associated Proteins metabolism
Neurons drug effects
Neurons radiation effects
Rats
Rats, Sprague-Dawley
Synapses drug effects
Vesicular Glutamate Transport Protein 2 metabolism
Hippocampus cytology
Long-Term Potentiation physiology
Matrix Metalloproteinase 9 physiology
Neurons physiology
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3077
- Volume :
- 98
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 17493927
- Full Text :
- https://doi.org/10.1152/jn.00202.2007