DEFICIENT LONG-TERM-MEMORY IN MICE WITH A TARGETED MUTATION OF THE CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN

The cAMP-responsive element-binding protein (CREB) has been implicated in the activation of protein synthesis required for long-term facilit ation, a cellular model of memory in Aplysia. Our studies with fear co nditioning and with the water maze show that mice with a targeted disr uption of the alpha and delta isoforms of CREB are profoundly deficien t in long-term memory. In contrast, short-term memory, lasting between 30 and 60 min, is normal. Consistent with models claiming a role for long-term potentiation (LTP) in memory, LTP in hippocampal slices from CREB mutants decayed to baseline 90 min after tetanic stimulation. Ho wever, paired-pulse facilitation and posttetanic potentiation are norm al. These results implicate CREB-dependent transcription in mammalian long-term memory.