Synaptic Organization of the Basolateral Amygdala

包括创伤后应激障碍（PTSD）在内的焦虑症影响着大约4000万美国人 成年人每年（18%的人口），因此是一个主要的健康问题。大脑的主要系统 与恐惧和焦虑有关的是杏仁核，包括它与离散前脑和脑干的联系 地区情绪的行为、电生理、药理和分子生物学研究 杏仁核的学习已经阐明了许多与正常恐惧有关的神经回路和机制 并提出了这些机制的改变可能引发焦虑的方式 紊乱然而，在更有效地利用这些机制之前， 可以开发治疗。这项拟议的研究是一项长期调查的继续， 杏仁核基底外侧核复合体（BLC）的突触组织，其主要目标是 阐明涉及情绪记忆的杏仁核系统的基本化学神经解剖学， 学习在本项目中，我们将集中于多巴胺能神经元输入的突触组织。 脑干系统，胆碱能和GABA能输入来自基底前脑，和 内侧前额叶皮层的脑电输入。在所有情况下，这些输入将被研究的关系 这些神经元亚群是在本基金先前的项目期间已经确定的。这些 研究将使用啮齿动物和猴子作为实验动物。尽管啮齿类动物已被用于大多数 情绪学习的功能研究，重要的是要确定非人类的突触组织是否 灵长类动物的杏仁核与此类似，因为它更像人类的杏仁核。这应该允许 关于灵长类动物BLC神经元的神经调节输入的组织信息被翻译成 开发新的药理学疗法来调节人杏仁核的活性， 神经精神和癫痫病症。在大鼠BLC中的研究将利用光学和电子显微镜来：1） 分析基底前脑胆碱能神经元和GABA能神经元对其的神经支配; 2）研究基底前脑胆碱能神经元和GABA能神经元对基底前脑的神经支配， 使用解剖学和生理学方法的D1和D2受体的亚细胞定位，和3） 研究内侧前额叶和颞叶皮质输入及其与多巴胺能输入的相互作用。 对猴子的研究将利用光学和电子显微镜来分析突触组织， 锥体细胞的多巴胺能神经支配、体细胞靶向中间神经元和树突靶向 BLC中的中间神经元。

Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. Behavioral, electrophysiological, pharmacological, and molecular biological studies of emotional learning in the amygdala have elucidated many of the neural circuits and mechanisms involved in normal fear and anxiety, and have suggested ways in which alterations in these mechanisms can provoke anxiety disorders. However, much more needs to be learned about these mechanisms before more effective treatments can be developed. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar systems involved in emotional memory and learning. In the present project we will focus on the synaptic organization of inputs from dopaminergic systems of the brainstem, cholinergic and GABAergic inputs from the basal forebrain, and glutamatergic inputs from the medial prefrontal cortex. In all cases these inputs will be studied in relation to specific neuronal subpopulations which have been identified in previous project periods of this grant. These studies will use both rodents and monkeys as experimental animals. Although rodents have been used in most functional studies of emotional learning, it is important to determine if the synaptic organization of the nonhuman primate amygdala is similar, since it is more likely to resemble that of humans. This should allow information about the organization of neuromodulatory inputs to primate BLC neurons to be translated into the development of novel pharmacological therapies to modulate the activity of the human amygdala in neuropsychiatric and epileptic disorders. Studies in the rat BLC will utilize light and electron microscopy to: 1) analyze its innervation by cholinergic and GABAergic neurons of the basal forebrain; 2) study the cellular and subcellular localization of D1 and D2 receptors using anatomical and physiological approaches, and 3) investigate medial prefrontal and temporal cortical inputs and their interactions with dopaminergic inputs. Studies in the monkey will utilize light and electron microscopy to analyze the synaptic organization and dopaminergic innervation of pyramidal cells, somatic-targeting interneurons, and dendritic-targeting interneurons in the BLC.