期刊
NEURAL PLASTICITY
卷 2014, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2014/128631
关键词
-
资金
- [R01-EY014882]
- [F31-NS079058]
Alzheimer's disease (AD) is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (A beta) peptides. Studies over the past few decades suggest that A beta is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for.. and beta-secretases, the two key enzymes that produce A beta by sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of A beta has been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity sensor, which acts upstream of A beta production and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronal beta-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.
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