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 facilitation, a cellular model of memory in Aplysia. Our studies with fear conditioning and with the water maze show that mice with a targeted disruption of the alpha and delta isoforms of CREB are profoundly deficient 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. However, paired-pulse facilitation and posttetanic potentiation are normal. These results implicate CREB-dependent transcription in mammalian long-term memory.
Bourtchuladze
R
R
Cold Spring Harbor Laboratory, New York 11724.
Frenguelli
B
B
Blendy
J
J
Cioffi
D
D
Schutz
G
G
Silva
A J
AJ
D000818:Animals; D001245:Association Learning; D003213:Conditioning, Psychological; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein