Brief Communication Reduced extinction of hippocampal-dependent memories in CPEB knockout mice

CPEB is a sequence-specific RNA binding protein that regulates translation at synapses. In neurons of CPEB knockout mice, synaptic efficacy is reduced. Here, we have performed a battery of behavioral tests and find that relative to wild-type animals, CPEB knockout mice, although similar on many baseline behaviors, have reduced extinction of memories on two hippocampal-dependent tasks. A corresponding microarray analysis reveals that about 0.14 % of hippocampal genes have an altered expression in the CPEB knockout mouse. These data suggest that CPEB-dependent local protein synthesis may be an important cellular mechanism underlying extinction of hippocampal-dependent memories. The modulation of synaptic strength, which underlies long-term memory storage (Hering and Sheng 2001), may involve “synaptic tagging, ” where a stimulated synapse is tagged with a molecular mark that a neuron uses to distinguish naive from stimulated synapses (Martin et al. 2000). Based on the recognition of this tag, a neuron can modify the strength of its synaptic response upon subsequent stimulation. While the nature of the tag is un-known, protein synthesis is involved in its establishment or rec