| Patterned activity and protein synthesis are both required for persistent changes in synaptic responses that shape neural circuits developmentally and form the basis for enduring memory later in life. It is not known, however, whether or how new protein synthesis contributes to synapse maturation or maintenance. Here, we show that brief periods of protein synthesis inhibition, applied globally or locally, produce a dramatic and use-dependent decrease in presynaptic vesicle reserve pool recycling and can destabilize synapses. CaM kinases are critical targets, as levels decrease within minutes and blocking their activity pharmacologically recapitulates effects of protein synthesis inhibition. As presynaptic terminals mature, PKA replaces CaM kinases. This developmental switch is controlled by the acquisition of A-kinase-anchoring proteins and coincides with decreased sensitivity to protein synthesis inhibition. These findings demonstrate a novel, developmentally-controlled stage of synapse maturation in which new protein synthesis rapidly and locally regulates activity at young synapses. |
