BACE1 is necessary for experience-dependent homeostatic synaptic plasticity in visual cortex
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 re...
| Veröffentlicht in: | Neural plasticity. - 1998. - 2014(2014) vom: 01., Seite 128631 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
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2014
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| Zugriff auf das übergeordnete Werk: | Neural plasticity |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural Cytoskeletal Proteins Nerve Tissue Proteins activity regulated cytoskeletal-associated protein Amyloid Precursor Protein Secretases EC 3.4.- Aspartic Acid Endopeptidases EC 3.4.23.- Bace1 protein, mouse |
| Zusammenfassung: | 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 |
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| Beschreibung: | Date Completed 06.10.2014 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1687-5443 |
| DOI: | 10.1155/2014/128631 |