Influence of stress in the structure and function of the amygdala
Year: 2008
Type: dissertation
Abstract: Stress is a powerful modulator of emotional behavior and is implicated in the etiology of mood disorders like anxiety, depression and phobias. Mood disorders are particularly common and affect a large percentage of the world population with relevant implications to individual’s health and to the society. Fear and anxiety represent specific aspects of emotional behavior that show behavioral resemblances but are triggered by events that activate distinct neuronal pathways: while the amygdala plays a key role in fear-conditioned to cue stimuli, the bed nucleus of the stria terminalis (BNST) is implicated in anxiety behavior and responses to contextual stimuli. In addition, the BNST is directly involved in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis being an important relay station of limbic inputs. In the present work, we have thoroughly characterized how emotional behavior, namely fear and anxiety, is affected by chronic stress. In order to uncover structural correlates of behavioral findings stereological estimates of the BNST and amygdaloid complex were performed, followed by 3-dimensional morphometric dendritic analysis. To clarify the relative importance of hormonal (corticosteroids) and central mediators (CRF1R or CRF2R agonists) of the stress response, and their contribution to neuroanatomical changes induced by stress, two additional sets of experiments were designed. Finally, the functional relevance of the observed changes was determined by characterizing the expression of immediate-early genes in control and stressed animals in basal conditions and after anxiogenic stimulus. Results show that chronic stress induces anxiety behavior without influencing fear-conditioning and locomotory/exploratory activity. Stress-induced anxiety correlated with increased volumes of the BNST, but not of the amygdala. Dendritic remodeling was found to make a significant contribution to the stress-induced increase in BNST volume, primarily due to changes in the anteromedial area of the BNST, an area strongly implicated in emotional behavior and in the neuroendocrine control of the stress response. Most of the effects of stress were recapitulated by exogenous corticosterone, while CRF1R reproduced particular aspects of spinogenesis. At last, chronic stress was associated to altered expression of c-fos in the BNST in both basal conditions and after anxiogenic stimuli. In conclusion, this study shows that chronic stress impacts on BNST structure and function establishing a possible correlation between anxiety behavior and structural remodeling. Finally, the functional impairment of the BNST may reflect the loss of inhibitory tone over the HPA and contribute to the perpetuation of corticosteroid neuronal restructuring.
Author: José Miguel Pêgo
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1574131994