title: BACE1 is necessary for experience-dependent homeostatic synaptic plasticity in visual cortex.
abstract: 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 (Aβ) peptides. Studies over the past few decades suggest that Aβ is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for β- and γ-secretases, the two key enzymes that produce Aβ by sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of Aβ 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 Aβ 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 β-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.
authors: Zanvyl-Krieger Mind/Brain Institute, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, 3400 N. Charles Street, Dunning Hall 348, Baltimore, MD 21218, USA.
authors: Emily
authors: 0000-0002-1364-1718
authors: E
authors: Petrus
authors: Zanvyl-Krieger Mind/Brain Institute, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, 3400 N. Charles Street, Dunning Hall 348, Baltimore, MD 21218, USA.
authors: Hey-Kyoung
authors: 0000-0002-5554-983X
authors: HK
authors: Lee
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology; D003627:Data Interpretation, Statistical; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D014793:Visual Cortex / Q000737:chemistry / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse