Synaptic Organization of the Basolateral Amygdala

基底外侧杏仁核的突触组织

• 批准号: 7652654
• 负责人: ALEXANDER JOSEPH MCDONALD
• 金额: $ 31.06万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7652654
• 关键词: Adult; Affect; American; Amygdaloid structure; Animals; Anxiety; Anxiety Disorders; Area; Behavioral; Biological; Brain; Brain Stem; Chemicals; Cholinergic Agents; Cholinergic Receptors; Complex; Development; Disease; Dopamine D1 Receptor; Dopamine D2 Receptor; Electron Microscopy; Electrons; Emotional; Epilepsy; Fright; Glutamates; Goals; Grant; Health; Human; Human Activities; Interneurons; Investigation; Learning; Light; Localized; Medial; Memory; Methods; Microscopic; Molecular; Monkeys; Muscarinic M2 Receptor; Muscarinics; Neuroanatomy; Neurons; Nuclear; Output; Parvalbumins; Physiological; Physiology; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Presynaptic Terminals; Primates; Prosencephalon; Pyramidal Cells; Rattus; Research Design; Rodent; Sensory; Somatostatin; Stress; Synapses; System; Temporal Lobe; Testing; Translating; basal forebrain; basal forebrain cholinergic neurons; cell type; cholinergic; nerve supply; neural circuit; neuropsychiatry; nonhuman primate; novel; research study

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.

焦虑症，包括创伤后应激障碍 (PTSD)，影响着约 4000 万美国人 每年都有成年人（占人口的 18%），因此是一个重大的健康问题。主要大脑系统 与恐惧和焦虑有关的是杏仁核，包括它与离散的前脑和脑干的联系 地区。情绪的行为、电生理学、药理学和分子生物学研究 杏仁核的学习阐明了与正常恐惧有关的许多神经回路和机制 和焦虑，并提出了这些机制的改变可能引发焦虑的方法 失调。然而，在更有效地实施之前，还需要对这些机制有更多的了解。 可以开发治疗方法。拟议的研究是长期调查的延续 杏仁核基底外侧核复合体（BLC）的突触组织，其主要目标是 阐明参与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，我们将重点关注多巴胺能输入的突触组织 脑干系统，来自基底前脑的胆碱能和 GABA 能输入，以及 来自内侧前额皮质的谷氨酸输入。在所有情况下，这些输入都将进行相关研究 针对在本次赠款的先前项目期间已确定的特定神经元亚群。这些 研究将使用啮齿动物和猴子作为实验动物。尽管大多数情况下都使用啮齿类动物 在情感学习的功能研究中，确定非人类的突触组织是否具有重要意义 灵长类动物的杏仁核也很相似，因为它更可能类似于人类的杏仁核。这应该允许 有关灵长类 BLC 神经元的神经调节输入的组织信息将被翻译成 开发新的药物疗法来调节人杏仁核的活性 神经精神和癫痫疾病。对大鼠 BLC 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和 GABA 能神经元的神经支配； 2）研究细胞和 使用解剖学和生理学方法对 D1 和 D2 受体进行亚细胞定位，以及 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和 锥体细胞、体细胞靶向中间神经元和树突靶向的多巴胺能神经支配 BLC 中的中间神经元。