The limbic system is composed of a group of brain structures associated with various functions, most notably emotion, cognition, fear, and motivation. There is considerable variation in what structures researchers consider to constitute the limbic system, though the two primary structures of the system are consistently noted to be the amygdala and hippocampus. It should be acknowledged that the concept of the limbic system as the predominant view of the limbic system as the locus of emotional regulation of emotional regulation is considered by many to be flawed because it is overly simplistic. Some researchers in mainstream psychology have suggested that the concept of the limbic system be abandoned altogether. Nonetheless, the key structures of the limbic system (i.e., the hippocampus and amygdala) play important regulatory roles in behavior and may factor into some of the psychological effects seen with exercise. Both the amygdala and hippocampus have demonstrated important links with emotion, cognition, and the adaptation to stress.
The Limbic System and the Stress Response
Perhaps one of the main reasons that the limbic system is associated with the stress response and behavior is because of the direct links that it shares with the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis, hippocampus, and amygdala (along with the autonomic nervous system [ANS] and dorsal raphe nuclei) all respond to stressful stimuli. Furthermore, these areas also influence corticotropin-releasing hormone (CRH), serotonin, and other endocrine responses associated with stressful stimuli. The stress responses appear to be mediated through mineralocorticoid and glucocorticoid receptors in target organs as well as in the limbic system itself. In conjunction with serotonergic input from the dorsal raphe nuclei, the amygdala and hippocampus help integrate cognitive and behavioral responses associated with the HPA axis during exposure to stressors, including exercise. Neuroanatomic pathways between the hippocampus and hypothalamus provide for integration of metabolic, emotional, and cognitive information.
As further evidence of the link between the limbic system and the HPA axis, glucocorticoids have structural and functional impacts on the hippocampus. Marked impairment of cognition has been noted with chronic exposure to stress. Additionally, chronic stress induces direct changes in CRH and CRH gene expression in the hippocampus as well as a variety of morphological changes associated with cognitive impairments. It appears that exercise, along with other positive stimuli such as an enriched environment, can counteract these deleterious effects and promote neurogenesis. Optimal challenge or stimulation positively influences limbic system development. An inverse-U relationship appears to exist for the effects of stress on hippocampal function and structure. Stressors of a moderate intensity, such as exercise, effectively enhance hippocampal-related cognitive function. On the other hand, excessive or chronic stressors impair cognition and, as noted previously, produce negative changes in the hippocampus and related gene expression.
The hippocampus plays a central role in regulating cognitive and endocrine responses and adaptations to stressors, including exercise. Part of this regulatory role is derived from the inhibition that the hippocampus exerts over HPA axis activation. It is also important for terminating HPA axis activity following stressor exposure in order to promote systemic recovery. The hippocampus exerts negative feedback on the paraventricular nucleus under situations of high glucocorticoid secretion in order to decrease CRH secretion. Additionally, there is a counter-regulatory influence by the glucocorticoids on hippocampal activity that results from acute stress. Under these conditions, the link between stress, the hippocampus, and the amygdala should also be recognized as stressors that impair the hippocampus yet enhance amygdala activation. This enhanced amygdala activation is particularly pronounced in the bed nucleus of the stria terminalis (BNST), which is a key projection site that has been associated with anxiety. Anxiety may manifest itself as such things as excessive worry and apprehension, physical tension, heightened cardiovascular tone, and, in animal models, freezing behaviors and decreased free-roaming.
Hippocampal Influences on Depression and Cognition
Dysfunction in the limbic system has been implicated in the development of depression and stress-related disorders. One of the mechanisms by which certain antidepressants appear to exert effects is through upregulation of neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), in the limbic structures. Further support for the link between the limbic system and depressive etiology is the fact that a number of morphological and metabolic changes occur in the hippocampus of individuals suffering from depression. It may partly be through this pathway that exercise exerts its effects on depression and anxiety. BDNF increases in the hippocampus in response to exercise and facilitates use-dependent neuronal growth. Despite the BDNF downregulation that is common during intense or prolonged stress, secretion is upregulated during exercise. Furthermore, there appear to be at least 33 exercise-regulated hippocampal genes, many of which are involved in growth factor and neurotrophic factor signaling and production. One growth factor in particular that is stimulated by exercise, VGF, appears to be involved in energy balance, synaptic plasticity, and has demonstrated antidepressant actions.
There is some evidence that brain uptake of insulin-like growth factor-1 (IGF-1) from endocrine or paracrine sources is necessary for exercise-induced hippocampal neurogenesis. Additionally, exercise helps halt the stress-induced efflux of glutamate from the hippocampus that can be detrimental to hippocampal structure and function. Activity-related increases in norepinephrine and serotonin may also have mediating roles in neurogenesis and cell proliferation, respectively.
The Amygdala: Emotion and Adaptation
The amygdala attributes emotional valence and arousal to external stimuli and integrates adaptive responses to stressors. The basolateral region of the amygdala integrates with the hippocampus to derive contextual information from stimuli. The centromedial area has projections to the lateral hypothalamus to help control blood pressure and projections to the BNST to regulate HPA activation. Because of these anatomical connections, amygdalar activation directly stimulates HPA axis responses and allows the limbic system to play a key role in regulating psychological and physiological adaptations to stressors, including exercise.
The amygdala plays a key role in emotional behaviors, fear conditioning, reward, and nociception. Much like the hippocampus, chronic stress can affect neuronal morphology and synaptic plasticity in the amygdala. This may be impacted significantly with exercise, though limited data currently exist to support this. The amygdalar CRH systems appear to be activated by stressors of a predominantly psychological nature, which may be related to cognitive interpretations of the nature of the exercise stimulus.
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