The role of stress and orexin in the development of behavioral phenotypes.

摘要

All forms of life experience stress. How individuals cope with stress is dependent on the type of stressor, their environment, life experiences, and genetic variability. While stress can serve as the impetus to adapt to an environment, in excess it is maladaptive. This work examines how changes in neural plasticity can yield variable behavioral coping strategies to stressors. An example of this variation can be seen in rats which do not all escape from an aggressive interaction when given the opportunity. In contrast, hamsters will always utilize an escape route to evade an aggressive individual. Two brain regions that we hypothesize are involved with different coping strategies to stressors are the amygdala and hippocampus. These are two brain areas that are also associated with formation of aversive memories and also heavily implicated in stress-related pathology such as anxiety disorders and depression. In stress disorders there is a reduction in both the size and function of the hippocampus with the opposite of this pattern in the amygdala. The expression of neurotrophic signaling factors in the hippocampus and amygdala of hamsters correlates with how quickly they escape. Orexin (also known as hypocretin) is involved in arousal states and anxiety responses. Orexin fibers also project to the hippocampus and amygdala which influence escape behavior in the stress choice model. Mice that displayed less depressive behavior had decreased orexin receptor expression in the amygdala in contrast to increased orexin in the hippocampus. Finally, chronic defeat which induces increases in depression and anxiety-associated behavior in accepted tests caused divergent expression patterns of the two known orexin receptors. Specifically, the type I receptor transcript (Orx1) was increased in the basolateral amygdala (BLA) while the type II (All forms of life experience stress. How individuals cope with stress is dependent on the type of stressor, their environment, life experiences, and genetic variability. While stress can serve as the impetus to adapt to an environment, in excess it is maladaptive. This work examines how changes in neural plasticity can yield variable behavioral coping strategies to stressors. An example of this variation can be seen in rats which do not all escape from an aggressive interaction when given the opportunity. In contrast, hamsters will always utilize an escape route to evade an aggressive individual. Two brain regions that we hypothesize are involved with different coping strategies to stressors are the amygdala and hippocampus. These are two brain areas that are also associated with formation of aversive memories and also heavily implicated in stress-related pathology such as anxiety disorders and depression. In stress disorders there is a reduction in both the size and function of the hippocampus with the opposite of this pattern in the amygdala. The expression of neurotrophic signaling factors in the hippocampus and amygdala of hamsters correlates with how quickly they escape. Orexin (also known as hypocretin) is involved in arousal states and anxiety responses. Orexin fibers also project to the hippocampus and amygdala which influence escape behavior in the stress choice model. Mice that displayed less depressive behavior had decreased orexin receptor expression in the amygdala in contrast to increased orexin in the hippocampus. Finally, chronic defeat which induces increases in depression and anxiety-associated behavior in accepted tests caused divergent expression patterns of the two known orexin receptors. Specifically, the type I receptor transcript (Orx1) was increased in the basolateral amygdala (BLA) while the type II (Orx2) was decreased. Furthermore, knocking down the Orx2 receptor with an adenovirus in the BLA of unstressed mice also induced anxiety behaviors which are associated with chronic defeat but not depressive behaviors. These results suggest that the orexin system has the ability to bidirectionally control anxiety disorders in the BLA and raises the possibility that an Orx2 receptor agonist may have potential as a novel treatment for anxiety.) was decreased. Furthermore, knocking down the Orx2 receptor with an adenovirus in the BLA of unstressed mice also induced anxiety behaviors which are associated with chronic defeat but not depressive behaviors. These results suggest that the orexin system has the ability to bidirectionally control anxiety disorders in the BLA and raises the possibility that an Orx2 receptor agonist may have potential as a novel treatment for anxiety.