Effects of protein inhibition on young and mature synaptic vesicle function
Inhibiting translation in hippocampal neurons for short periods of time (2 hours) has differential presynaptic effects based on the cell's developmental time frame. In young neurons it inhibits induction of LTP and leads to reductions in the pool of available vesicles for exocytosis, which is exacerbated by synaptic activity.
In mature neurons, the effects are dependent upon the size of the styryl dye loading site. If the loading site where synaptic vesicle release is measured is less than 1.35 µm2, then the effects of protein translation are similar to young neurons (i.e., reductions in pool of available vesicles). But if the loading site is >1.35 µm2, then the fluorescence dye intensity is not affected much by protein translation inhibition, indicating that their synaptic vesicle recycling pools are unchanged by inhibition of translation.
Sebeo et al used control vehicle (V.), anisomycin (A.), and cycloheximide (C.) on hippocampal cell neurons, the latter two of which inhibit protein translation in cultured hippocamapal neurons. Here is a diagram showing the results of fluorescence intensity following these treatments:
The authors suggest that the reason for this threshold (!) effect is that a different mechanism is used by the younger sites, where CaMKII leads to vesicle recycling. This is opposed to the larger sites of mature neurons, where protein kinase A is localized to regulate vesicle recycling. It's possible, though, that the reality is more continuous and that protein kinase A / A-kinase anchor proteins are merely upregulated at larger mature sites.
On the other hand, postsynaptic functioning is unaffected by inhibition of protein translation, as indicated by similar EPSC response curves in neurons treated with vehicle and anisomycin:
The effects of protein translation inhibition could mimic the effects of selective downregulation during development and thus represents a mech by which certain synapses could be pruned. It also suggests that, short-term, protein synthesis itself is essential to synaptic function only in so far as the pool of synaptic vesicles needs to be recycled.
Reference
Sebeo J, et al. 2009 Requirement for Protein Synthesis at Developing Synapses. doi:10.1523/JNEUROSCI.2613-09.2009