Graded fear generalization enhances the level of cfos‐positive neurons specifically in the basolateral amygdala. Issue 12 (23rd September 2016)

• Record Type: Journal Article
• Authors: Rajbhandari, Abha K.; Zhu, Ruoyan; Adling, Cora; Fanselow, Michael S.; Waschek, James A.
• Other Names: Ghiani Cristina A. guestEditor.; Prager Eric M. guestEditor.
• Is Part Of: Journal of neuroscience research. Volume 94:Issue 12(2016)
• Page Start: 1393
• Page End: 1399
• Publication Date: 2016-09-23
• Subjects: fear conditioning -- fear generalization -- amygdala; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.23947
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract : Fear is an important emotional reaction in response to threatening stimuli and is important for survival. However, when fear occurs in inappropriate circumstances, it can lead to pathological conditions including an increased vulnerability for developing anxiety disorders such as posttraumatic stress disorder (PTSD). Patients with PTSD generalize fear to contexts or to environments that are not associated with the trauma. We sought to explore if increasing the level of dissimilarity relative to the context in which mice learn fear results in changes in the level of fear responding to the new context. We also determined with this procedure if the number of cells expressing the immediate early gene cfos changes with the corresponding level of expressed fear within brain regions known to be important in modulating fear, including the basolateral amygdala (BLA) and hippocampus. Our results indicate that mice that were tested in increasingly different contexts showed significantly different levels of fear responses. Freezing level was higher in the context most similar to the acquisition context than the one that was highly different. The level of cfos within the BLA, but not hippocampus, was also significantly different between the test contexts, with higher levels in the somewhat similar compared with the most different context. Overall, these results highlight the BLA as a critical region in the node of fear circuitry for modulating fear generalization. © 2016 Wiley Periodicals, Inc. Abstract : While fear is critical for survival to react to threatening stimuli, inappropriately high levels of fear lead to pathological conditions including posttraumatic stress disorder. Using enhanced fear in a rodent model, our findings show that mice that acquire an enhanced level of fear show significantly higher levels of freezing in a novel context that most closely resembles the context where the fear was originally acquired. In these mice, neuronal activity is also augmented within the basolateral nuclei of the amygdala (BLA). However, freezing and levels of neuronal activity were lower in the context that was most dissimilar to the fear acquisition context. This indicates that BLA is an important region in which enhanced fear generalization leads to increased neuronal activity.