Synaptic Organization of the Basolateral Amygdala

描述（由申请人提供）：焦虑症，包括创伤后应激障碍（PTSD），每年影响大约4000万美国成年人（占人口的18%），因此是一个主要的健康问题。与恐惧和焦虑有关的主要大脑系统是杏仁核，包括它与前脑和脑干区域的连接。对杏仁核中情绪学习的研究已经确定了许多与正常恐惧和焦虑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症的方法。然而，在开发出更有效的治疗方法之前，需要对这些回路进行更多的了解。本研究是对大鼠杏仁核基底外侧核复合体（BLC）突触组织的长期研究的延续，其主要目的是阐明涉及情绪（包括情绪学习）的杏仁核回路的基本化学神经解剖学。在本项目中，我们关注脑干和基底前脑的三个递质特异性神经调节系统输入的突触组织。这些包括脑干的去甲肾上腺素能和多巴胺能系统，以及基底前脑的胆碱能/ gaba能输入。尽管这些系统在杏仁核情绪功能的生理和病理生理上很重要，但使用最先进的多标记光和电子显微镜方法对这些电路的研究很少。特异性目的1将分析基底前脑胆碱能神经元和gaba能神经元对BLC的神经支配。特异性目标#2将研究锥体细胞的神经支配和不同的神经间亚群通过去肾上腺素能输入到BLC。具体目标#3将检查BLC的多巴胺能神经支配，以及它与多巴胺受体和颞叶皮层谷氨酸能感觉输入的相互作用。本研究的首要假设是，投射到BLC的独立神经调节系统对情绪记忆亚功能进行了分割，这将涉及不同神经调节系统对离散神经元亚群和区室的不同靶向，以及不同神经元亚群中不同受体亚型的表达。焦虑症，包括创伤后应激障碍（PTSD），每年影响大约4000万美国成年人（占人口的18%），因此是一个主要的健康问题。与恐惧和焦虑有关的主要大脑系统是杏仁核，包括它与前脑和脑干区域的连接。本研究是对大鼠杏仁核基底外侧核复合体（BLC）突触组织的长期研究的延续，其主要目的是阐明参与情绪的杏仁核系统的基本化学神经解剖学。

DESCRIPTION (provided by applicant): 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. Studies of emotional learning in the amygdala have identified 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 circuits 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 rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar circuits involved in emotion, including emotional learning. In the present project we focus on the synaptic organization of inputs from three transmitter-specific neuromodulatory systems of the brainstem and basal forebrain. These include noradrenergic and dopaminergic systems of the brainstem, as well as the cholinergic/GABAergic inputs from the basal forebrain. Despite the importance of these systems for the physiology and pathophysiology of amygdalar emotional function, there have been few studies of these circuits using state-of-the-art multiple- labeling light and electron microscopic methods. Specific Aim #1 will analyze the innervation of the BLC by cholinergic and GABAergic neurons of the basal forebrain. Specific Aim #2 will study the Innervation of pyramidal cells and distinct interneuronal subpopulations by noradrenergic inputs to the BLC. Specific Aim #3 will examine the dopaminergic innervation of the BLC, and its interactions with dopamine receptors and glutamatergic sensory inputs from the temporal cortex. The overarching hypothesis of this research is that there is a parcellation of emotional mnemonic subfunctions subserved by separate neuromodulatory systems projecting to the BLC, and that this will involve the differential targeting of discrete neuronal subpopulations and compartments by different neuromodulatory systems, and by the expression of different receptor subtypes in distinct neuronal subpopulations. 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. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar systems involved in emotion.