Abstract
The current view of the molecular basis for information storage is that post‐translational modification (PTM) of brain proteins is important for the early stages of memory storage and that protein synthesis is necessary for long‐lasting memory. This view has been challenged by the proposal that PTM of synaptic proteins is the critical instructive mechanism underlying both recent as well as long‐lasting memories (Routtenberg and Rekart,2005). As an initial test, a broad spectrum serine/threonine kinase inhibitor (H‐7) was delivered bilaterally to rat anterior cingulate cortex 1 h before a 3 week retention test of contextual fear conditioning. This significantly blocked 21‐Day retention. In the second experiment evaluating extinction of a 21‐Day remote memory, H‐7 injected into mouse medial prefrontal cortex blocked fear extinction. As the H‐7‐induced impairment in 21‐Day retention was indexed by a decrease in freezing, while the extinction blockade by no decrease in freezing, the results could not be ascribed to a direct effect of the drug on behavioral performance. This represents the first demonstration, to our knowledge, that PTM inhibition, here serine/threonine kinase activity, interferes with long‐lasting memory, providing initial support for the PTM model. © 2006 Wiley‐Liss, Inc.