Post-translational synaptic protein modification as substrate for long-lasting, remote memory: an initial test.
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.
Holahan
Matthew R
MR
Department of Psychology, Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208, USA. matthew_holahan@carleton.ca
Routtenberg
Aryeh
A
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000033:anatomy & histology; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000502:physiology*; D017397:Prefrontal Cortex; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases