Control of the establishment of aversive memory by calcineurin and Zif268.
Emotional memory is a rapidly acquired and persistent form of memory, and its robustness is in part determined by the initial strength of the memory. Here, we provide new evidence that the protein phosphatase calcineurin (CaN), a potent negative regulator of neuronal signaling that is known to constrain learning and memory, critically regulates the establishment of emotional memory through mechanisms involving the immediate early gene Zif268 (also known as Egr1). We found that CaN is inhibited in the amygdala during the establishment of aversive memory, but Zif268 is activated. Using inducible transgenesis in mice, we further saw that CaN inhibition and Zif268 overexpression during memory establishment strengthen the memory trace and enhance its resistance to extinction. We found that CaN inhibition correlates with increased Zif268 expression and that a common pool of proteins is regulated in the amygdala after CaN inhibition and Zif268 overexpression. Together, these findings reveal a previously unknown mechanism for the control of emotional memory that depends on CaN and Zif268.
Baumgärtel
Karsten
K
Brain Research Institute, Medical Faculty of the University of Zürich and Department of Biology, Swiss Federal Institute of Technology, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Genoux
David
D
Welzl
Hans
H
Tweedie-Cullen
Ry Y
RY
Koshibu
Kyoko
K
Livingstone-Zatchej
Magdalena
M
Mamie
Céline
C
Mansuy
Isabelle M
IM
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D004644:Emotions / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019703:Calcineurin