Effects of matrix metalloproteinase inhibition on short- and long-term plasticity of schaffer collateral/CA1 synapses.
It is increasingly evident that matrix metalloproteinases (MMPs), a family of zinc containing extracellular endopeptidases, participate in processes supporting hippocampal synaptic plasticity. The purpose of this study was to further the understanding of MMPs involvement in hippocampal plasticity. Acute hippocampal slices, generated from 20- to 30-day-old male Sprague-Dawley rats, were subjected to various electrophysiologic stimulatory paradigms to produce either short-term or long-term modifications to synaptic efficacy. Slices exposed to broad-spectrum MMP inhibitor, FN-439, exhibited impairments in paired-pulse facilitation, theta-burst facilitation, and long-term depression. Additionally, we observed that MMP inhibition impaired both the induction and stability of long-term potentiation (LTP). Furthermore, evidence indicated that the effect of MMP inhibition on LTP maintenance is dependent upon integrin-directed adhesion, whereas the effects of MMP inhibition on LTP induction are independent of integrin-directed adhesion. Together, these data support a generalized role for MMPs in short-term and long-term hippocampal plasticity and indicate that MMPs are a necessary facet of integrin-mediated cell adhesion supporting LTP stabilization.
Meighan
Peter C
PC
Departments of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USADepartment of Psychology, Washington State University, Pullman, Washington, USA.
Meighan
Starla E
SE
Departments of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USADepartment of Psychology, Washington State University, Pullman, Washington, USA.
Davis
Christopher J
CJ
Departments of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USADepartment of Psychology, Washington State University, Pullman, Washington, USA.
Wright
John W
JW
Departments of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USADepartment of Psychology, Washington State University, Pullman, Washington, USA.
Harding
Joseph W
JW
Departments of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USADepartment of Psychology, Washington State University, Pullman, Washington, USA.
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000201:enzymology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000201:enzymology*; D013826:Theta Rhythm / Q000187:drug effects; D013997:Time Factors
C095170:4-aminobenzoyl-glycyl-prolyl-leucyl-alanine hydroxamic acid; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D016023:Integrins; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D020782:Matrix Metalloproteinases