Distinctive roles for amygdalar CREB in reconsolidation and extinction of fear memory

Abstract

Cyclic AMP response element binding protein (CREB) plays a critical role in fear memory formation. Here we determined the role of CREB selectively within the amygdala in reconsolidation and extinction of auditory fear. Viral overexpression of the inducible cAMP early repressor (ICER) or the dominant-negative mCREB, specifically within the lateral amygdala disrupted reconsolidation of auditory fear memories. In contrast, manipulations of CREB in the amygdala did not modify extinction of fear. These findings suggest that the role of CREB in modulation of memory after retrieval is dynamic and that CREB activity in the basolateral amygdala is involved in fear memory reconsolidation.

Figure 1.

Amygdalar CREB is required for fear memory reconsolidation. (A) mCREB overexpression in the BLA disrupts auditory fear memory after retrieval (*) P < 0.05; (B) fear memory retrieval is not disrupted without prior reactivation. (C) ICER overexpression in the BLA disrupts memory after retrieval (*) P < 0.05; (D) fear memory retrieval is not disrupted without prior reactivation; (A–D) open symbols represent baseline freezing in Context B. Neither HSV-mCREB (□) nor HSV-ICER (○) altered baseline freezing.

Figure 2.

Amygdalar CREB is not required for extinction of auditory fear. (A) Expression of mCREB or (B) overexpression of CREB during retrieval does not alter extinction of conditioned fear.

Figure 3.

Expression of HSV-LacZ in the amygdala. For confirmation of viral expression, rats were transcardially perfused with 10% formalin 72 h after injection. Immunohistochemistry of 15-μm slide-mounted sections was conducted using a previously published protocol (Chao et al. 2002). Antibodies: goat anti-β-galactosidase (β-gal) (1:5000 Biogenesis England, UK); Cy3-conjugated secondary antibodies (1:200 Jackson ImmunoResearch, USA). DAPI (1:10000).