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%），因此是一个重大的健康问题。涉及恐惧和焦虑的主要大脑系统是杏仁核，包括它与离散的前脑和脑干区域的连接。对杏仁核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，还需要对这些回路有更多的了解。拟议的研究是对大鼠杏仁核基底外侧核复合体（BLC）突触组织长期研究的延续，其主要目标是阐明参与情绪（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，我们重点关注来自脑干和基底前脑的三个特定递质神经调节系统的输入的突触组织。这些包括脑干的去甲肾上腺素能和多巴胺能系统，以及来自基底前脑的胆碱能/GABA能输入。尽管这些系统对于杏仁核情绪功能的生理学和病理生理学很重要，但很少有使用最先进的多重标记光和电子显微镜方法对这些回路进行研究。具体目标#1 将分析基底前脑胆碱能和 GABA 能神经元对 BLC 的神经支配。具体目标#2 将研究 BLC 去甲肾上腺素能输入对锥体细胞和不同中间神经元亚群的神经支配。具体目标#3 将检查 BLC 的多巴胺能神经支配，及其与多巴胺受体和来自颞叶皮层的谷氨酸感觉输入的相互作用。这项研究的总体假设是，存在由投射到 BLC 的单独神经调节系统维护的情感助记子功能的分割，这将涉及不同神经调节系统对离散神经元亚群和区室的差异定位，以及通过表达不同的神经元亚群中存在不同的受体亚型。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（占总人口的 18%），因此是一个重大的健康问题。涉及恐惧和焦虑的主要大脑系统是杏仁核，包括它与离散的前脑和脑干区域的连接。拟议的研究是对大鼠杏仁核基底外侧核复合体（BLC）突触组织长期研究的延续，其主要目标是阐明参与情绪的杏仁核系统的基本化学神经解剖学。