Graduate Training in Neuroscience
University of Washington
Daniel R. Storm
Professor, Department of Pharmacology
A striking feature of memory is the persistence of long-term memory which can last for periods exceeding the lifetimes of synaptic proteins.
Consolidation of hippocampus-dependent memory depends upon Ca2+activation of the cAMP/Erk MAP kinase (MAPK) /CREB transcriptional
pathway and de novo protein synthesis. Stimulation of MAPK activity positively regulates CREB-mediated transcription and protein synthesis during
memory formation. Activation of CRE-mediated transcription in the hippocampus depends upon the calmodulin (CaM)-stimulated adenylyl
cyclases which generate a cAMP signal necessary for the activation of MAPK. Our current research is based upon recent discoveries made
by our lab including the discovery that that the cAMP/MAPK/ CRE transcriptional pathway undergoes a circadian oscillation in area CA1 of the
hippocampus and that disruption of this signaling oscillation days after memory consolidation decreases the persistence of memory.
Furthermore, we discovered that this memory consolidation pathway is activated during REM sleep relative to awake animals. This suggests that
hippocampus-dependent memories are maintained over extended periods of time by periodic reactivation of CREB-mediated transcription
during the circadian cycle, during sleep, and that these events are driven by cAMP activation of MAPK. We hypothesize that this critical cAMP
signal is generated by CaM stimulated adenylyl cyclases. We propose that neurons stimulated during the acquisition of hippocampus-dependent
memory that contribute to the initial memory trace may be periodically reactivated during the circadian cycle, during REM sleep.