Synaptic Organization of the Basolateral Amygdala

基底外侧杏仁核的突触组织

基本信息

批准号：
8267068
负责人：
ALEXANDER JOSEPH MCDONALD
金额：
$ 30.68万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-07-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8267068
关键词：
Adult Affect American Amygdaloid structure Anxiety Anxiety Disorders Area Brain Brain Stem Brain region Characteristics Chemicals Cholinergic Receptors Complex Data Development Disease Dopamine D1 Receptor Dopamine D2 Receptor Dopamine Receptor Electron Microscopy Electrons Emotional Emotions Fluorescence Fright Functional disorder Glutamates Goals Grant Health Immunohistochemistry Investigation Ion Channel Label Learning Light Methods Microscopic Muscarinic M1 Receptor Muscarinic M2 Receptor Muscarinics Neuroanatomy Neuromodulator Neurons Neurotransmitters Noise Nuclear Output Physiology Population Positioning Attribute Post-Traumatic Stress Disorders Prefrontal Cortex Presynaptic Terminals Prosencephalon Pyramidal Cells Rattus Research Role Sensory Signal Transduction Stress Synapses Synaptic plasticity System Techniques Temporal Lobe Testing basal forebrain cell type cholinergic design effective therapy executive function light microscopy neglect nerve supply neural circuit neuromechanism neuronal excitability neuropsychiatry neurotransmitter release noradrenergic novel receptor

项目摘要

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.

描述（由申请人提供）：焦虑症，包括创伤后应激障碍（PTSD），每年影响约4000万美国成年人（占人口的18％），因此代表了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，包括与离散的前脑和脑干区域的联系。杏仁核中情绪学习的研究已经确定了许多涉及正常恐惧和焦虑的神经回路和机制，并提出了这些机制改变可以引起焦虑症的方法。但是，在开发更有效的治疗方法之前，需要了解更多有关这些电路的知识。拟议的研究是对大鼠杏仁核基底外侧核复合物（BLC）的突触组织进行长期研究，其主要目标是阐明参与情感的杏仁核电路的基本化学神经解剖结构，包括情感学习。在本项目中，我们关注来自脑干和基础前脑的三个发射器特异性神经调节系统的突触组织。其中包括脑干的去甲肾上腺素能和多巴胺能系统，以及基础前脑的胆碱能/GABA能输入。尽管这些系统对于杏仁核情绪功能的生理和病理生理学很重要，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。特定的目标＃1将通过基础前脑的胆碱能和GABA能神经元分析BLC的神经。特定的目标＃2将研究金字塔细胞的神经和对BLC的甲肾上腺素能输入的明显的神经元亚群。特定的目标＃3将检查BLC的多巴胺能神经支配，以及其与颞皮层的多巴胺受体和谷氨酸能感觉输入的相互作用。这项研究的总体假设是，通过投射到BLC的单独的神经调节系统所提供的情感助记符亚功能的拟合，这将涉及不同受体neuronyplepes in Dienters neuronrone nimerronepece nifter neuron timplepes nifter neuronron的差异靶向离散的神经元亚群和剖面的差异靶向。焦虑症，包括创伤后应激障碍（PTSD），每年影响约4000万美国成年人（占人口的18％），因此代表了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，包括与离散的前脑和脑干区域的联系。拟议的研究是对大鼠杏仁核基底外侧核复合物（BLC）的突触组织进行长期研究，其主要目标是阐明参与情感的杏仁核系统的基本化学神经解剖学。