Long lasting effects of predator stress on pCREB expression in brain regions involved in fearful and anxious behavior

Predator stress is one animal model of posttraumatic stress disorder (PTSD). Neural plasticity in amygdala afferent and efferent pathways underlies anxiogenic effects of predator stress. Predator stress increases pCREB expression in these pathways 20 min after stress, implicating pCREB in stress-induced neural plasticity. Here we examined impact of predator stress on pCREB expression 6–24 h and 7 days after stress in amygdala pathways and in the supramammillary nucleus (SuM). Patterns of change in pCREB expression were complex, time dependent, column dependent in the periaqueductal gray (PAG), and AP plane dependent in the amygdala. In contrast to past work at 20 min after stress, there were no stress-induced increases in pCREB in the amygdala in the anterior AP plane or in the lateral PAG at 6 h onward after stress. However, dorsal PAG pCREB was increased bilaterally at 24 h and 7 days after stress. In the mid AP plane of all amygdala nuclei there were bilateral stress-induced increases in pCREB at 6 h followed by decreases at 24 h post stress. A similar pattern was observed in the posterior AP plane. In addition, we found a persistent increase (6 h to 7 days after stress) in pCREB expression in the SuM. Further study of this nucleus as a contributor to fear sensitization following predator stress is warranted. Overall, these data highlight persistent neuroplastic changes in key brain areas following traumatic stress. Identification of these changes may aid in understanding the neural mechanisms underlying acquired anxiety disorders such as PTSD.

► Predator stress alters amygdala (AM), periaqueductal gray (PAG) pCREB 20 min after stress.
► Here we studied AM, PAG and supramammillary nucleus pCREB expression at 6–24 h and 7 days after stress.
► Patterns of change in pCREB expression were complex and time dependent.
► Patterns of change were also column dependent in the PAG, and AP plane dependent in the amygdala.
► Changes lasted from 24 h to 7 days depending on the brain area.