A Synaptic Locus Controlling Behavioral Depression

 描述（由申请人提供）：抑郁症是一种常见疾病，可导致人类显著的发病率和死亡率。目前尚不清楚潜在的分子、细胞或电路机制。目前，治疗性干预在机制上还没有得到很好的理解，而且往往不成功。重要的是要从机制上理解抑郁症，以便开发有效的治疗方法。 大脑中参与奖励系统的部分被认为起着重要的作用。外侧缰（LHb）是奖励回路的重要组成部分，它提供“奖励预测错误”信号：当动物收到的奖励低于预期（即失望）或预期会受到惩罚（即预期会有不好的事情发生）时，LHb是活跃的，通常认为这些信息会用来塑造未来的行为，以最大化奖励并避免不愉快的事件。一个过度活跃的LHb的人会很容易或持续地感到失望，通常会有不好的结果。因此，许多对人类和啮齿动物的研究表明，LHb的过度活动会导致重度抑郁症，这并不奇怪。这项拨款旨在研究LHb中的信息如何在正常啮齿动物中处理，并通过与抑郁症相关的操作进行修改。

 DESCRIPTION (provided by applicant): Depression is a common disease that causes significant morbidity and mortality in humans. There is currently no clarity regarding the underlying molecular, cellular or circuit mechanisms. Presently, therapeutic intervention is not well understood mechanistically and often unsuccessful. It is important to derive a mechanistic understand of depressive disorders so that effective treatment can be developed. Abnormalities in parts of the brain that participate in the reward system are thought to play important roles. The lateral habenula (LHb) is an important part of the reward circuit by providing `reward prediction error' signals: when an animal receives a reward that is less than expected (i.e. is disappointed) or anticipates punishment (i.e. expects something bad), the LHb is active, and this information is thought normally to be used to shape future behavior to maximize reward and avoid unpleasant events. An individual with overly active LHb would be expected to be easily or continually disappointed and generally expect bad outcomes. It is therefore not a surprise that a number of studies in humans and rodents indicate that excessive activity in the LHb contributes to major depression. This grant proposes to examine how information in the LHb is processed in normal rodents, and modified by manipulations related to depression.