Grant: Project Grant

Adapting to external stress is essential for animal survival, but becomes problematic when the stress is intense or unrelenting. In humans, post-traumatic stress disorder, anxiety disorders and depressive disorders can all connect to previous stressful experiences. A fundamental aspect of the stress response involves altering body energy metabolism in response to stress hormones released by the adrenal glands. In the brain, support cells called astrocytes provide energy molecules to nerve cells, thereby helping to feed synapses - the communication points between nerve cells. This process is necessary for learning and memory and proper brain health. Importantly, stress interferes with the ability of synapses to store memories, yet a potential role for astrocytes in this well-appreciated phenomenon is not known. A central question driving our research forward is: how does the energetic support of nerve cells by astrocytes participate in the responses to external stress? Using advanced genetic and physiological techniques to study mouse brains after a bout of intense stress, our preliminary findings have discovered that the delivery of energy molecules from astrocytes to nerve cells is compromised, which prevents memory formation. This leads us to test the idea that astrocytes help regulate the brain's response to stress by gating synaptic memory via the supply of energy molecules to synapses. This proposal will reveal a new understanding for how intense or prolonged stress changes the brain. This is important because novel stress related mechanisms will be uncovered and potential therapeutic targets for stress-related disorders will be identified.