Synaptic function and plasticity are crucial for information processing within the nervous system. In glutamatergic hippocampal neurons, presynaptic function is silenced, or muted, after strong or prolonged depolarization. This muting is neuroprotective, but the underlying mechanisms responsible for muting and its reversal, unmuting, remain to be clarified. Using cultured rat hippocampal neurons, we found that muting induction did not require protein synthesis; however, slow forms of unmuting that depend on protein kinase A (PKA), including reversal of depolarization-induced muting and forskolin-induced unmuting of basally mute synapses, required protein synthesis. In contrast, fast unmuting of basally mute synapses by phorbol esters was protein synthesis-independent. Further studies of recovery from depolarization-induced muting revealed that protein levels of Rim1 and Munc13-1, which mediate vesicle priming, correlated with the functional status of presynaptic terminals. Additionally, this form of unmuting was prevented by both transcription and translation inhibitors, so proteins are likely synthesized
Publisher: Public Library of Science
Date Published: 13-December-2012
Author(s): Crawford D., Jiang X., Taylor A., Moulder K., Mennerick S.