Journal ArticleDOI
Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system
TLDR
It is found that activity regulates postsynaptic composition and signaling through the ubiquitin-proteasome system, providing a mechanistic link between synaptic activity, protein turnover and the functional reorganization of synapses.Abstract:
Experience-dependent remodeling of the postsynaptic density (PSD) is critical for synapse formation and plasticity in the mammalian brain. Here, in cultured rat hippocampal neurons, I found long-lasting, global changes in the molecular composition of the PSD dictated by synaptic activity. These changes were bidirectional, reversible, modular, and involved multiple classes of PSD proteins. Moreover, activity-dependent remodeling was accompanied by altered protein turnover, occurred with corresponding increases or decreases in ubiquitin conjugation of synaptic proteins and required proteasome-mediated degradation. These modifications, in turn, reciprocally altered synaptic signaling to the downstream effectors CREB (cyclic AMP response element binding protein) and ERK-MAPK (extracellular signal regulated kinase-MAP kinase). These results indicate that activity regulates postsynaptic composition and signaling through the ubiquitin-proteasome system, providing a mechanistic link between synaptic activity, protein turnover and the functional reorganization of synapses.read more
Citations
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Journal ArticleDOI
LTP and LTD: an embarrassment of riches.
Robert C. Malenka,Mark F. Bear +1 more
TL;DR: This work reviews those forms of LTP and LTD for which mechanisms have been most firmly established and examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function.
Journal ArticleDOI
Homeostatic plasticity in the developing nervous system
TL;DR: Evidence is discussed from a number of systems that homeostatic synaptic plasticity is crucial for processes ranging from memory storage to activity-dependent development, and how these processes maintain stable activity states in the face of destabilizing forces is discussed.
Journal ArticleDOI
Experience-dependent structural synaptic plasticity in the mammalian brain.
Anthony Holtmaat,Karel Svoboda +1 more
TL;DR: Recent evidence for structural forms of synaptic plasticity in the mammalian cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively.
Journal ArticleDOI
Regulation of NMDA receptor trafficking by amyloid-beta.
Eric M. Snyder,Yi Nong,Claudia G. Almeida,Surojit Paul,Timothy D. Moran,Eun Young Choi,Angus C. Nairn,Angus C. Nairn,Michael W. Salter,Paul J. Lombroso,Gunnar K. Gouras,Paul Greengard +11 more
TL;DR: It is found that application of amyloid-β promoted endocytosis of NMDA receptors in cortical neurons, indicating a new mechanism by which amyloids-β can cause synaptic dysfunction and contribute to Alzheimer disease pathology.
Journal ArticleDOI
The Self-Tuning Neuron: Synaptic Scaling of Excitatory Synapses
TL;DR: Current evidence suggests that neurons detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites.
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