PT - JOURNAL ARTICLE AU - Newton H. Woo AU - Peter V. Nguyen TI - Protein Synthesis Is Required for Synaptic Immunity to Depotentiation AID - 10.1523/JNEUROSCI.23-04-01125.2003 DP - 2003 Feb 15 TA - The Journal of Neuroscience PG - 1125--1132 VI - 23 IP - 4 4099 - http://www.jneurosci.org/content/23/4/1125.short 4100 - http://www.jneurosci.org/content/23/4/1125.full SO - J. Neurosci.2003 Feb 15; 23 AB - De novo protein synthesis and transcription are necessary for the expression of long-lasting synaptic potentiation [long-term potentiation (LTP)] in hippocampal area CA1 and for the consolidation of long-term memory. The stability of LTP and its longevity require macromolecular synthesis at later stages, but a specific role for early protein synthesis has not been identified. Using electrophysiological recording methods in mouse hippocampal slices, we show that multiple trains of high-frequency stimulation provide immediate synaptic immunity to depotentiation. This immunity to depotentiation is dependent on the amount of synaptic stimulation used to induce LTP, it is input specific, and it is prevented by inhibitors of protein synthesis. We propose that local translation mediates input-specific synaptic immunity against depotentiation. We also present evidence suggesting that, in addition to translation, products of transcription can provide cell-wide immunity to depotentiation via heterosynaptic transfer of synaptic immunity between distinct pathways in area CA1. Protein synthesis and transcription may importantly regulate long-term storage of information by conferring synaptic immunity to depotentiation at previously potentiated synapses.