Effects of NPY on Hippocampal Circuit Function

神经肽Y（NPY）具有强大的抗焦虑（抗焦虑）特性，并被认为是一种压力恢复力 因子临床和临床前研究表明，NPY信号调节应激依赖性行为， 包括人类和啮齿动物。我们对NPY影响突触和回路功能的机制的了解 改变行为是不完整的神经肽Y与多种焦虑症有关，包括焦虑症后抑郁症。 创伤性应激障碍（PTSD）。在创伤后应激障碍患者和动物中检测到低水平的NPY 暴露在创伤压力下已经提出调节NPY作为PTSD和其他疾病的潜在疗法。 焦虑症海马体与包括创伤后应激障碍在内的焦虑症有关， 被认为是不适应的学习形式。神经肽Y及其受体在海马体中处于高水平， 将NPY直接注射到海马中减弱啮齿动物的回避行为。重要的是， 海马中的NPY在暴露于创伤应激的啮齿动物中减少。这背后的机制 下降是未知的。然而，创伤应激导致的NPY表达减少是重要的，因为 海马内注射NPY可减轻行为症状。在上一个融资期，我们展示了 创伤性应激导致海马CA1区颞氨通路中NPY释放的丧失， 海马体，这是一条对记忆巩固和恐惧学习很重要的通路。在这段时间里，我们 将确定TA通路中NPY释放对海马回路功能和行为的影响， 研究创伤应激引起的NPY释放减少的机制，并测试是否增强 TA通路中NPY的释放可以挽救创伤应激的行为效应。这些研究可以 导致新的治疗策略，以减轻创伤后应激障碍患者的焦虑症状。

Neuropeptide Y (NPY) has robust anxiolytic (anti-anxiety) properties and is thought to be a stress resilience factor. Clinical and pre-clinical studies have shown that NPY signaling regulates stress-dependent behavior in both humans and rodents. Our knowledge of the mechanisms by which NPY affects synaptic and circuit function to alter behavior is incomplete. NPY has been implicated in a wide variety of anxiety disorders, including post- traumatic stress disorder (PTSD). Low levels of NPY have been measured in patients with PTSD and in animals exposed to traumatic stress. Modulation of NPY has been proposed as a potential therapy for PTSD and other anxiety disorders. The hippocampus has been implicated in anxiety disorders including PTSD, which can be considered maladaptive forms of learning. NPY and its receptors are found at high levels in hippocampus, and direct injections of NPY into hippocampus attenuate avoidance behavior in rodents. Importantly, the levels of NPY in hippocampus are reduced in rodents exposed to traumatic stress. The mechanism underlying this decrease is not known. However, the reduction in NPY expression by traumatic stress is important, because injection of NPY into hippocampus alleviates behavioral symptoms. In the previous funding period, we showed that traumatic stress causes the loss of NPY release in the temporammonic pathway in the CA1 region of hippocampus, a pathway that is important for memory consolidation and fear learning. In this funding period, we will determine the effects of NPY release in the TA pathway on hippocampal circuit function and behavior, investigate the mechanisms of decreased NPY release caused by traumatic stress, and test whether enhancing release of NPY in the TA pathway can rescue the behavioral effects of traumatic stress. These studies could lead to new therapeutic strategies to alleviate anxiety symptoms in PTSD patients.