Soldiers at war can be injured by explosive blasts and sometimes the injuries do not involve an open wound. That is, the wave of pressure produced by an explosion can disrupt the way the brain functions in ways that are not completely understood. Soldiers at war can also suffer injury from the intense psychological stress of battle. In such a case, serious depression and anxiety can result from the traumatic experiences that can have a major and long-lasting effect on the quality of life of the individual. The processes that lead to such depression after traumatic experiences are also not completely understood. This proposal is aimed at better understanding the basic processes by which these adverse effects occur. Soldiers can encounter both traumatic experiences and explosive blasts on the battlefield, so we are especially interested in gaining a better understanding of how these combined factors can produce injury. Because of their extreme nature, exposure to these events cannot occur in the laboratory using people, but instead, animal models are used that represent, to some degree, what can happen in people. The results from the proposed studies will give us information to increase our understanding of how these injuries occur. This increased understanding, in turn, can lead to the design of better treatments for the injury in the form of new drugs and new therapies. The information can also lead to better protection from the injuries. While the proposal is specifically designed to address questions that occur on the battlefield, the information gained is also beneficial to the civilian population as they too can be exposed to similar events and suffer similar injuries.