Editors' ChoiceNeurobiology

Memories of the Proteasome

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Science's STKE  24 Oct 2006:
Vol. 2006, Issue 358, pp. tw363
DOI: 10.1126/stke.3582006tw363

The process of long-term potentiation (LTP) in the hippocampus­­­--a stable change in synaptic strength after stimulation of a neuronal circuit--is thought to provide a cellular mechanism for learning and memory. Late-phase LTP (L-LTP), the longest lasting form of such plasticity, is inhibited when protein synthesis is blocked, which has led investigators to propose that there may be newly synthesized proteins that account for the changes in cellular function. In the most simple terms, one might expect, then, that inhibition of the proteasome, which mediates degradation of proteins tagged with the peptide ubiquitin, might enhance L-LTP. In keeping with some earlier indications, however, Fonseca et al. found that pharmacological inhibition of the proteasome inhibited L-LTP in cultured hippocampal slices from rat brain. Unexpectedly, if a protein synthesis inhibitor was applied along with the proteasome inhibitor, L-LTP was restored. The authors propose that rather than an absolute requirement for generation of new proteins, it may be a balance of degradation and synthesis that is most important to enable long-lasting changes in synaptic plasticity. Not discussed by the authors is the additional possibility that recently described more direct effects of the proteasome on transcription could factor into the explanation for these results.

R. Fonseca, R. M. Vabulas, F. U. Hartl, T. Bonhoeffer, U. V. Nägerl, A balance of protein synthesis and proteasome-dependent degradation determines the maintenance of LTP. Neuron 52, 239-245 (2006). [PubMed]

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