Stress Hardware Reviews: The Hippocampus

clip_image001What brain structures rouse us from inactivity and set in motion our defense mechanisms when a stressor is perceived? Predictably, the brain’s older and more primordial area, the so-called animal brain, where the hypothalamus, the amygdala, the hippocampus, the septum area, the basal ganglia and the thalamus are located. These structures, collectively called the limbic system, are interconnected and work together to initiate motor and other functional activities of the brain that mobilize the body. In this post about stress hardware, we discuss the hippocampus.

Virtually any experience perceived by the five senses appears to cause the activation of at least some part of the hippocampus. The hippocampus in turn redistributes these sensory signals to the thalamus, the hypothalamus, and other parts of the limbic system. Thus, the hippocampus acts as an important switching center through which incoming sensory signals are retransmitted and initiate behavioral reactions for different purposes. Its importance has been demonstrated empirically: experimental artificial stimulation of the hippocampus can induce a wide variety of behavioral patterns such as pleasure, rage, passivity, or excessive sexual drive.

The cells of the hippocampus appear to be especially sensitive to the effects of various stressors. Although not directly involved in the stress response, its ventral regions appear to exercise a regulatory influence on the hypothalamic-pituitary-adrenal (HPA) axis activity and are also a primary target for elevated glucocorticoid levels. The glucocorticoid hormones owe their name to their important effects on blood glucose concentration, which is the principal source of energy of the human cell. They also regulate protein and fat consumption, and the utilization of carbohydrates to produce additional quantities of energy. Cortisol is the principal glucocorticoid.
Several animal studies have shown that the exposure to unpredictable stressors or to a new environment can cause a quite rapid activation of the hippocampus. On the other hand, predictability and familiarity in early life can help create a more modulated response to stressful events. For example, in rats, postnatal handling increases later hippocampal tolerance to stress. Animals handled in early life show reduced stress-induced HPA activity as adults. In particular, increased maternal licking/grooming during early life enhances glucocorticoid negative feedback sensitivity, decreases hypothalamic stimulation of cortisol release, and produces a lower HPA responses to stress. It is hypothesized, although not yet proven experimentally, that secure infant attachment through good enough nurturing by the primary caregiver can have a protective effect, enabling the individual to respond more adaptively to future life stressors thanks to a higher stress tolerance.

The hippocampus is one of the most important pathways from the “reward” and “punishment” areas of the limbic system. Sensory stimuli or thoughts that cause pain or aversion excite the limbic punishment centers, and stimuli that cause pleasure, happiness, or sense of reward excite the limbic reward centers. Taken together, they provide the background mood and motivations of the person. One of these motivations is the drive to remember experiences and thoughts that are either pleasant or unpleasant. The hippocampus appears to be particularly important in deciding which thoughts are important enough to be worthy of memory, on a basis of their association with either reward or punishment experiences. For example, it is believed that the hippocampus and its many connections with the limbic behavioral system are responsible for the development of an absolute aversion to foods that have caused nausea and vomiting.

The hippocampus is essential for declarative memory, which is the voluntary recollection of previous learned information. In humans, as in rodents, elevated glucocorticoids can compromise hippocampal function and cause cognitive impairments. A study of elderly healthy individuals examined cognitive function in relation to individual differences in HPA activity and hippocampal integrity. High cortisol levels were associated with cognitive impairment, such as deficits in spatial learning and memory, and a higher degree of hippocampal damage. Prolonged exposure to high glucocorticoid levels damages hippocampal integrity and negatively affects learning and memory. Thus, high levels of stress early in life (as in a situation of neglect or abuse), or chronic levels of stress later in life both contribute to a near-constant state of high cortisol level in the limbic system, with predictable negative effects on learning, memory, stress management and overall functioning.