Neurobiology of learning and memory
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Neurobiol Learn Mem · Jul 2014
ReviewStress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.
A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. ⋯ Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of strong long-term memories because the activation of hippocampal GRs after learning is coupled to the recruitment of the growth and pro-survival BDNF/cAMP response element-binding protein (CREB) pathway, which is well-know to be a general mechanism required for long-term memory formation. We will then speculate about how these results may explain the negative effects of traumatic or chronic stress on memory and cognitive functions.
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Neurobiol Learn Mem · Jul 2014
ReviewThe downside of strong emotional memories: how human memory-related genes influence the risk for posttraumatic stress disorder--a selective review.
A good memory for emotionally arousing experiences may be intrinsically adaptive, as it helps the organisms to predict safety and danger and to choose appropriate responses to prevent potential harm. However, under conditions of repeated exposure to traumatic stressors, strong emotional memories of these experiences can lead to the development of trauma-related disorders such as posttraumatic stress disorder (PTSD). This syndrome is characterized by distressing intrusive memories that can be so intense that the survivor is unable to discriminate past from present experiences. ⋯ Finally, we summarize a selection of studies indicating that genetic variations found to be associated with enhanced fear conditioning, reduced fear extinction or better episodic memory in human experimental studies can have clinical implications in the case of trauma exposure and influence the risk of PTSD development. Here, we focus on genes involved in noradrenergic (ADRA2B), serotonergic (SLC6A4), and dopaminergic signaling (COMT) as well as in the molecular cascades of memory formation (PRKCA and WWC1). This is supplemented by initial evidence that such memory-related genes might also influence the response rates of exposure-based psychotherapy or pharmacological treatment of PTSD, which underscores the relevance of basic memory research for disorders of altered memory functioning such as PTSD.
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Neurobiol Learn Mem · Jul 2014
ReviewThe role of glucocorticoids, catecholamines and endocannabinoids in the development of traumatic memories and posttraumatic stress symptoms in survivors of critical illness.
Critically ill patients are at an increased risk for traumatic memories and post-traumatic stress disorder (PTSD). Memories of one or more traumatic events play an important part in the symptom pattern of PTSD. Studies in long-term survivors of intensive care unit (ICU) treatment demonstrated a clear and vivid recall of traumatic experiences and the incidence and intensity of PTSD symptoms increased with the number of traumatic memories present. ⋯ A number of small studies have demonstrated that the administration of cortisol to critically ill or injured patients results in a significant reduction of PTSD symptoms after recovery without influencing the number of traumatic memories. These glucocorticoid effects can possibly be explained by a cortisol-induced temporary impairment in traumatic memory retrieval which has previously been demonstrated in both rats and humans. The hypothesis that stress doses of glucocorticoids or the pharmacologic manipulation of glucocorticoid-endocannabinoid interaction during traumatic memory consolidation and retrieval could be useful for prophylaxis and treatment of PTSD after critical illness should be tested in larger controlled studies.
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Neurobiol Learn Mem · Jul 2014
Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.
Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6 h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. ⋯ Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context.