Selective erasure of a fear memory.
Memories are thought to be encoded by sparsely distributed groups of neurons. However, identifying the precise neurons supporting a given memory (the memory trace) has been a long-standing challenge. We have shown previously that lateral amygdala (LA) neurons with increased cyclic adenosine monophosphate response element-binding protein (CREB) are preferentially activated by fear memory expression, which suggests that they are selectively recruited into the memory trace. We used an inducible diphtheria-toxin strategy to specifically ablate these neurons. Selectively deleting neurons overexpressing CREB (but not a similar portion of random LA neurons) after learning blocked expression of that fear memory. The resulting memory loss was robust and persistent, which suggests that the memory was permanently erased. These results establish a causal link between a specific neuronal subpopulation and memory expression, thereby identifying critical neurons within the memory trace.
Han
Jin-Hee
JH
Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Kushner
Steven A
SA
Yiu
Adelaide P
AP
Hsiang
Hwa-Lin Liz
HL
Buch
Thorsten
T
Waisman
Ari
A
Bontempi
Bruno
B
Neve
Rachael L
RL
Frankland
Paul W
PW
Josselyn
Sheena A
SA
D000647:Amnesia / Q000503:physiopathology*; D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D003213:Conditioning, Psychological; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005239:Fear; D008568:Memory / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein