ausblenden:
Schlagwörter:
Action Potentials/physiology
Animals
Cells, Cultured
Cobalt/metabolism
Dendrites/*metabolism
Excitatory Amino Acid Agonists/metabolism
Excitatory Postsynaptic Potentials/*physiology
Hippocampus/cytology/metabolism
Homeostasis
In Vitro Techniques
Nerve Tissue Proteins/*biosynthesis
Patch-Clamp Techniques
Protein Subunits/metabolism
Rats
Receptors, AMPA/metabolism
Receptors, N-Methyl-D-Aspartate/metabolism
Signal Transduction/physiology
Synapses/*physiology
Synaptic Transmission/*physiology
Zusammenfassung:
Activity deprivation in neurons induces a slow compensatory scaling up of synaptic strength, reflecting a homeostatic mechanism for stabilizing neuronal activity. Prior studies have focused on the loss of action potential (AP) driven neurotransmission in synaptic homeostasis. Here, we show that the miniature synaptic transmission that persists during AP blockade profoundly shapes the time course and mechanism of homeostatic scaling. A brief blockade of NMDA receptor (NMDAR) mediated miniature synaptic events ("minis") rapidly scales up synaptic strength, over an order of magnitude faster than with AP blockade alone. The rapid scaling induced by NMDAR mini blockade is mediated by increased synaptic expression of surface GluR1 and the transient incorporation of Ca2+-permeable AMPA receptors at synapses; both of these changes are implemented locally within dendrites and require dendritic protein synthesis. These results indicate that NMDAR signaling during miniature synaptic transmission serves to stabilize synaptic function through active suppression of dendritic protein synthesis.
