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Publication : Prepulse inhibition and fear-potentiated startle are altered in tissue inhibitor of metalloproteinase-2 (TIMP-2) knockout mice.

First Author  Jaworski DM Year  2005
Journal  Brain Res Volume  1051
Issue  1-2 Pages  81-9
PubMed ID  15979591 Mgi Jnum  J:99752
Mgi Id  MGI:3583720 Doi  10.1016/j.brainres.2005.05.057
Citation  Jaworski DM, et al. (2005) Prepulse inhibition and fear-potentiated startle are altered in tissue inhibitor of metalloproteinase-2 (TIMP-2) knockout mice. Brain Res 1051(1-2):81-9
abstractText  The ability to discriminate between potential dangers and recall those stimuli is essential for survival. This emotional learning requires the involvement of higher brain structures, including the amygdala, hippocampus and related cortical structures. Long-term changes in synaptic transmission and structure are important for the establishment and consolidation of fear memory. The structural changes associated with this synaptic plasticity likely require alterations in the composition of the extracellular matrix (ECM). ECM integrity is maintained by the opposing action of matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). To date, no studies have examined the role of MMPs or TIMPs in conditioned fear. Here, we show that neither male nor female mice deficient in TIMP-2 (knockout) exhibit prepulse inhibition of the startle reflex, suggesting deficits in pre-attentional sensorimotor gating. In addition, knockout mice and mice expressing a mutant truncated TIMP-2 (knock-down) show deficits in fear-potentiated startle. This is the first report of a phenotype for the TIMP-2(-/-) mice and suggests that TIMP-2 may play a role in the synaptic plasticity underlying learning and memory.
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