Does Stress Damage the Brain? Bruce S. McEwen, PhD

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	Slide 7: The amygdala and hippocampus work together to provide the memory for events associated with strong emotions. Click for: AUDIO   FULL TEXT
	Slide 8: Emotionally-charged memories are strengthened by the actions of acutely secreted stress hormones. Click for: AUDIO   FULL TEXT
	Slide 9: Stress hormones have both beneficial and damaging effects: the rest of the lecture will elaborate on these. Click for: AUDIO   FULL TEXT
	Slide 10: The Morris Water Maze: rodents learn the shortest path to safety. Click for: AUDIO   FULL TEXT
	Slide 11: Another way we know how glucocorticoids work is from their effects on electrical activity and acquisition of contextual information. Click for: AUDIO   FULL TEXT
	Slide 12: Glucocorticoids also facilitate an action of serotonin to enhance GABA inhibition. Click for: AUDIO   FULL TEXT
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FULL TEXT OF SLIDES, Below 7. The amygdala and hippocampus work together to provide the memory for events associated with strong emotions. The hippocampus provides the "context" - ie, the events and places - that become strongly associated with the emotionally-charged memory. 8. Emotionally-charged memories are strengthened by the actions of acutely secreted stress hormones. Blocking beta adrenergic receptors outside of the blood-brain barrier reduces the strength of memory in a passive avoidance task in rats. Blocking glucocorticoid receptors at a number of locations within the brain (eg. Hippocampus, amygdala, nucleus of the solitary tract (NTS)) weakens the strength of those same types of memories (Roozendaal, 2000). On the other hand, there is a negative side when stress is prolonged. For example, chronic psychosocial stress, that is, being a subordinate male vervet monkey in a dominance hierarchy over many months, results in signs of atrophy and damage of neurons within the hippocampus (Uno et al., 1989). This suggests that prolonged and severe stress can damage the brain. 9. Thus stress hormones have both beneficial and damaging effects, and the rest of the lecture will elaborate on both of these outcomes. The first topic is the enhancement of memory and related functions by stress hormones. 10. In the Morris Water Maze, a rat or mouse learns to find the shortest path in a tank of water in order to swim to safety on a platform hidden beneath the water surface. The most challenging aspect is to use global spatial cues to find the hidden platform's location. Glucocorticoid hormones have a beneficial effect in this type of learning, and this has been shown by studies that have inactivated the glucocorticoid receptor. For example, recent work has shown that transgenic mice lacking the DNA binding domain of GR fail to learn the Morris Water Maze hidden platform task either with or without glucocorticoids (Oitzl et al., 2001). 11. Another way that we know how glucocorticoids work in the hippocampus is from their effects on electrical activity, on the one hand, and the acquisition of contextual information, on the other. Primed-burst potentiation in the CA1 region shows an inverted U dose-response to corticosterone, with enhanced activity at low to moderate levels and inhibition at high levels (Diamond et al., 1992). The acquisition of contextual information for fear conditioning to context ( ie. Recognizing a chamber where a shock is subsquently administered) shows enhancement at low doses of corticosterone and suppression back to baseline at higher levels (Pugh et al., 1997). Although not shown on this figure, higher levels of glucocorticoids suppress hippocampal-dependent memory below baseline in both animals and humans. 12. Glucocorticoids also facilitate an action of serotonin to enhance GABA inhibitory control over sensory input to the lateral amygdala (Stutzmann et al., 1998).