Protein synthesis inhibitor reduces late-phase long-term potentiation in hippocampus

Cool study by Je et al, using genetically engineered specific inhibition of eIF2 - alpha mediated protein synthesis to study the role of de novo protein synthesis in neurons. Late-phase long-term potentiation (L-LTP) in  hippocampal slices was shown in 1988 to be dependent upon protein synthesis by general protein inhibition, but it has remained unclear whether the inhibition is due to changes in presynaptic CA3 neurons or postsynaptic CA1 neurons. With their fast-acting  virally transduced system, they were able to show that specifically inhibiting protein synthesis in CA1 (i.e., postsynaptic) neurons reduces L-LTP following theta burst stimulation as compared to controls. But, crucially, similar treatment in the CA3 region did not inhibit LTP, strongly suggesting that L-LTP is dependent upon postsynaptic protein synthesis. From what I can tell, this is consistent with our understanding of postsynaptic changes and lends importance to the current search for tagging systems that tell the nucleus to transport newly synthesized proteins to specific dendrites.

Reference

Je HS, et al. 2009 Chemically inducible inactivation of protein synthesis in genetically targeted neurons. Journal of Neuroscience 29:6761-6766. doi:10.1523/JNEUROSCI.1280-09.2009.