Continuing the search for the engram: examining the mechanism of fear memories

Continuing the search for the engram: examining the mechanism of fear memories


J Psychiatry Neurosci 2010; 35(4): 221-228

Sheena A. Josselyn, PhD

Program in Neurosciences and Mental Health, The Hospital for Sick Children, and the Department of Physiology and Institute of Medical Sciences, University of Toronto, Toronto, Ont.


The goal of my research is to gain insight using rodent models into the fundamental molecular, cellular and systems that make up the base of memory formation. My work focuses on fear memories. Aberrant fear and/or anxiety may be at the heart of many psychiatric disorders. In this article, I review the results of my research group; these results show that particular neurons in the lateral amygdala, a brain region important for fear, are specifically involved in particular fear memories. We started by showing that the transcription factor CREB (cAMP/Ca2+ response element binding protein) plays a key role in the formation of fear memories. Next, we used viral vectors to overexpress CREB in a subset of lateral amygdala neurons. This not only facilitated fear memory formation but also “drove” the memory into the neurons with relatively increased CREB function. Finally, we showed that selective ablation of the neurons overexpressing CREB in the lateral amygdala selectively erased the fear memory. These findings are the first to show disruption of a specific memory by disrupting select neurons within a distributed network.

Submitted Jan. 22, 2010; Revised Apr. 7, 2010; Accepted Apr. 12, 2010.

Acknowledgments: In this review, I outlined my scientific journey. Of course, I did not take this journey alone, as all the work described here has been a team effort. I mentioned many of the important people along the way. I would also like to specifically acknowledge certain individuals whose contributions were vital. First, my postdoctoral mentors, Mike Davis and Alcino Silva. Next, the members of my laboratories (both past and present), especially Jin-Hee Han, Adelaide Yiu, Christy Cole and Hwai-Lin (Liz) Hsiang. Finally, I thank my collaborators, Eric Nestler, Bill Carlezon, Rachael Neve and John Guzowski, and especially Steven Kushner and Paul Frankland. I would like to thank the people in my lab and my many collaborators for making this work possible. I would also like to thank Paul W. Frankland for suggestions on this manuscript. This work was supported by Canadian Institutes of Health Research (MOP74650), EJLB Foundation and grants from the National Sciences and Engineering Research Council of Canada.

Competing interests: None declared

DOI: 10.1503/jpn.100015

Correspondence to: Dr. S.A. Josselyn, The Hospital for Sick Children, 555 University Ave., Toronto ON M5G 1X8; fax 406 813-7717;