Enabling Stress Resistance

描述（由申请人提供）：虽然大多数人在面对压力时能够保持心理完整，但众所周知，压力经历会引发严重神经精神疾病的发作和复发，包括重度抑郁症和创伤后应激障碍。社会压力对几乎所有哺乳动物物种都是常见的，啮齿类动物的慢性从属压力通常伴随着一种长期行为综合症的表达，包括社交回避、快感缺乏、对其他环境压力的应对反应受损以及焦虑样行为。在近交系小鼠C57BL/6J中，并非所有遭受慢性社会失败压力的个体都出现显著表达的应激诱导综合征，从而允许测量弹性。据推测，这些结果表明，小鼠之间的个体差异介导了对慢性应激有害影响的易感性或抵抗力。然而，这一假设缺乏明确的验证

DESCRIPTION (provided by applicant): Though most individuals are capable of maintaining psychological integrity in the face of stress, stress-experiences are well known for instigating th onset and relapse of severe neuropsychiatric disorders including MDD and PTSD. Social stress is common to practically all mammalian species, and chronic subordination stress in rodents is most often followed by the expression of a long-lasting behavioral syndrome that includes social avoidance, anhedonia, impaired coping responses to other environmental stressors, and anxiety-like behaviors. Within the inbred strain of mouse C57BL/6J, the prominently expressed stress-induced syndrome does not occur in all individuals subjected to chronic social defeat stress, thereby allowing for measurements of resiliency. Presumably, these results suggest that individual differences across mice mediate the susceptibility or resistance to the deleterious effects of chronic stress. Nevertheless, unequivocal validation of this hypothesis is lacking since the majority of studies aimed at investigating susceptibility to chronic stress are based on experiments performed in mice that have been previously exposed to chronic stress, or mice that are subjected to molecular manipulations prior to stress exposure (ultimately altering normal brain function).Here were propose to use multi-circuit in vivo recording in conjunction with circuit selective modulation using designer receptors exclusively activated by designer drugs (DREADDs) to characterize the circuit based mechanisms that mediate resistance to stress in C57BL/6J mice. The rationale that underlies the proposed research is that variations in cortical-amygdala circuit function will be associated with stress responses, and that direct modulation of this circuit will alter stress resistance across mice. This strategy will provide an unprecedented circuit level of understanding of how stress exposure ultimately alters activity across neural circuits that regulate fear and reward processing and reveal new circuit based targets for therapeutic intervention for mood and anxiety disorders.