Neighborhood matters: divergent patterns of stress-induced plasticity across the brain

Abstract

The fact that exposure to severe stress leads to the development of psychiatric disorders serves as the basic rationale for animal models of stress disorders. Clinical and neuroimaging studies have shown that three brain areas involved in learning and memory--the hippocampus, amygdala and prefrontal cortex--undergo distinct structural and functional changes in individuals with stress disorders. These findings from patient studies pose several challenges for animal models of stress disorders. For instance, why does stress impair cognitive function, yet enhance fear and anxiety? Can the same stressful experience elicit contrasting patterns of plasticity in the hippocampus, amygdala and prefrontal cortex? How does even a brief exposure to traumatic stress lead to long-lasting behavioral abnormalities? Thus, animal models of stress disorders must not only capture the unique spatio-temporal features of structural and functional alterations in these brain areas, but must also provide insights into the underlying neuronal plasticity mechanisms. This Review will address some of these key questions by describing findings from animal models on how stress-induced plasticity varies across different brain regions and thereby gives rise to the debilitating emotional and cognitive symptoms of stress-related psychiatric disorders.

LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior

“…Stress is known to affect the plasticity and excitability of the hippocampus (27). Together with the amygdala and prefrontal cortex, the hippocampus is part of the complex circuitry involved in mammalian trait anxiety, and its substantial role has been acknowledged (5,7,8,28). We show that in the hippocampus, LSD1/neuroLSD1 repression of plasticity genes can be exerted in association with the transcription factor SRF.…”

“…Seminal studies have shown that mice experiencing different forms of stress, including psychosocial stress, promote stress-related plasticity through epigenetic changes at specific genes, including brain-derived neurotrophic factor (BDNF) and immediate early genes (IEGs) (2)(3)(4). These modifications induce contrasting structural and functional changes in the hippocampus and the amygdala (5), brain areas responsible for the expression of anxiety-like behavior (5)(6)(7)(8). A decrease in neural activity in the hippocampus caused by the loss of dendritic arbors and spines is associated with posttraumatic stress disorder and recurrent depressive illness (5).…”

“…These modifications induce contrasting structural and functional changes in the hippocampus and the amygdala (5), brain areas responsible for the expression of anxiety-like behavior (5)(6)(7)(8). A decrease in neural activity in the hippocampus caused by the loss of dendritic arbors and spines is associated with posttraumatic stress disorder and recurrent depressive illness (5). Therefore, an important challenge for molecular psychiatry is a better understanding of the epigenetic regulation of plasticity gene transcription in response to stress (9).…”

On antidepressants and still feeling low

“…It also plays a central role in the stress response, both promoting downstream hypothalamic-pituitaryadrenal (HPA) axis stimulation and receiving HPA axis feedback (8). Engagement of the stress system can fundamentally change amygdala structure and function, especially as a result of ELS (2,(9)(10)(11). Moreover, the amygdala is likely a component of the neural circuit involved in antidepressant action (12,13), and the antidepressant response is modified by prior stress exposure (10,14).…”

“…For example, stress paradigms that induce depressive-like behaviors result in hypertrophy of the amygdala, potentially through an increase of dendritic arborizations and spines (1,9). Parallel physiological changes contribute to a sensitization of amygdala engagement (9).…”