NEURAL SYSTEMS INVOLVED IN THE REDUCTION OF FEAR

正如在创伤后应激障碍（PTSD）中观察到的那样，一次创伤经历可能导致过度广泛性恐惧的发展。为了理解创伤后应激障碍和相关疾病，使用动物模型的基础研究集中在确定负责巴甫洛夫条件恐惧的获得和表达的神经回路上。然而，在临床上，这些疾病的一个主要问题是无法减少或抑制创伤记忆和相关的焦虑。因此，一个重要的研究领域是关于减少或抑制不想要的记忆的方式，以及为什么在创伤性恐惧条件反射之后这一点如此困难。很少有基础研究检查负责减少恐惧的神经回路。私家侦探的长期目标他的研究是：(1)识别和检查与减少恐惧有关的神经回路；(2)评估是否像在创伤后应激障碍中观察到的那样，过度的恐惧可以被理解为通常减少恐惧的过程的中断。拟议的研究将使用处于恐惧条件抑制程序中的大鼠来确定负责减少恐惧的神经回路。在这个过程中，一个刺激（如灯光）获得了产生恐惧的能力，而另一个刺激（如噪音）获得了减少恐惧的能力。因为条件抑制的神经回路必须对恐惧减少刺激提供的传入感觉输入作出反应，实验将确定处理听觉恐惧减少刺激的听觉结构。对条件抑制回路的这种“感觉肢体”的识别将为未来的建议提供一个起点，这些建议将识别负责恐惧条件抑制的回路的其他组件。这个项目将是第一个系统地评估与减少恐惧有关的神经回路，并将为进一步研究与减少恐惧有关的大脑机制和神经递质提供基础。这项工作的结果将提供重要的新信息，将进一步加深我们对创伤后应激障碍和相关疾病的理解，并可能导致新的和更有效的治疗这些疾病。

A single traumatic experience can result in the development of overgeneralized fear, as observed in Posttraumatic Stress Disorder (PTSD). To understand PTSD and related disorders, basic research using animal models has focused on identifying the neural circuits that are responsible for the acquisition and expression of Pavlovian conditioned fear. Clinically, however, a major problem seen in these disorders is an inability to reduce or inhibit the traumatic memories and the associated anxiety. Hence, an important area of inquiry concerns the way unwanted memories can be reduced or inhibited and why this is so difficult following traumatic fear conditioning. There has been very little basic research examining neural circuits responsible for reducing fear. The long term goals of the P.I.'s research are to (1) identify and examine the neural circuits involved in the reduction of fear and (2) assess whether exaggerated fear, as observed in PTSD, can be understood in terms of a disruption in the processes that normally reduce fear. The proposed research will use rats in a conditioned inhibition of fear procedure to identify the neural circuit responsible for the reduction of fear. In this procedure, one stimulus (e.g., a light) acquires the ability to produce fear while another stimulus (e.g., a noise) acquires the ability to reduce fear. Because the neural circuit for conditioned inhibition must be responsive to afferent sensory input provided by the fear reducing stimulus, experiments will identify the auditory structures that process the auditory fear reducing stimulus. Identification of this "sensory limb" of the conditioned inhibition circuit will provide a starting point for future proposals that will identify other components of the circuit responsible for conditioned inhibition of fear. This project will be the first to systematically evaluate the neural circuits involved in the reduction of fear and will provide the foundation for further examining the brain mechanisms and neurotransmitters involved in the reduction of fear. The results of this work will provide important new information that will further our understanding of PTSD and related disorders and may lead to new and more effective treatments for these disorders.