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Science 13 March 2009:
Vol. 323. no. 5920, pp. 1492 - 1496
DOI: 10.1126/science.1164139
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Reports

Selective Erasure of a Fear Memory

Jin-Hee Han,1,2,3 Steven A. Kushner,1,4 Adelaide P. Yiu,1,2 Hwa-Lin (Liz) Hsiang,1,2 Thorsten Buch,5 Ari Waisman,6 Bruno Bontempi,7 Rachael L. Neve,8 Paul W. Frankland,1,2,3 Sheena A. Josselyn1,2,3*

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.

1 Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
2 Institute of Medical Sciences, University of Toronto, Toronto, ON, M5G 1X8, Canada.
3 Department of Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada.
4 Department of Psychiatry, Erasmus University Medical Center, 3015 CE Rotterdam, Netherlands.
5 Department of Pathology, University of Zurich, CH-8057 Zurich, Switzerland.
6 I.Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, 55131 Mainz, Germany.
7 Centre de Neurosciences Intégratives et Cognitives, CNRS UMR5228 and University of Bordeaux 1, 33405 Talence, France.
8 Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: sheena.josselyn{at}sickkids.ca

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Science. ISSN 0036-8075 (print), 1095-9203 (online)