Journal
BRAIN RESEARCH
Volume 1051, Issue 1-2, Pages 81-89Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2005.05.057
Keywords
extracellular matrix; fear conditioning; learning; MMP; synaptic plasticity; TIMP
Categories
Funding
- NCRR NIH HHS [P20 RR16435] Funding Source: Medline
- NINDS NIH HHS [NS045225, R29 NS035874-05, R29 NS035874-04S1, R01 NS045225-01A2, NS35874] Funding Source: Medline
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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. (c) 2005 Elsevier B.V. All rights reserved.
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