Synaptic Organization of the Basolateral Amygdala

描述（由申请方提供）：拟定研究是对基底外侧杏仁核（ABL）的神经元和突触组织进行长期研究的继续。它将侧重于通过递质特异性神经调质系统对ABL中间神经元的调节。目标#1将根据肽和钙结合蛋白的含量来鉴定灵长类动物ABL中的中间神经元亚群。这些标志物将用于识别目标2和3中的每个亚群。目标#2将使用综合解剖/生理实验来确定不同的神经元间亚群是否表现出不同的电生理特征。此外，负责这些电生理功能的离子通道将使用免疫组织化学技术进行定位。目的#3将通过多巴胺能、去甲肾上腺素能和多巴胺能传入分析ABL神经元亚群的神经支配。还将使用综合解剖学-生理学/药理学方法确定特定的神经元间亚群是否表现出特异性5-羟色胺受体。目的#4将分析胆碱能轴突对ABL中间神经元亚群的神经支配，并确定哪些中间神经元表达烟碱型与毒蕈碱型胆碱能受体。 在啮齿动物中进行的其他解剖学研究将检验以下假设：ABL与新皮质和海马一样，含有GABA能神经元的子集，这些神经元从基底前脑的GABA能投射神经元接收输入并向其提供输出。这些拟议的研究包括第一次全面分析的电生理特性，确定ABL interneuronal亚群在啮齿动物和灵长类动物的脑切片。此外，将研究5-羟色胺和多巴胺能药物对这些神经元中关键电生理特性的调节。这些研究将有助于了解ABL中的抑制机制，并对开发新的药物治疗以调节ABL在癫痫和精神疾病中的活性至关重要。

DESCRIPTION (provided by applicant): The proposed study is the continuation of a long-term investigation of the neuronal and synaptic organization of the basolateral amygdala (ABL). It will focus on the regulation of ABL interneurons by transmitter-specific neuromodulator systems. Aim #1 will identify subpopulations of interneurons in the primate ABL on the basis of their content of peptides and calcium-binding proteins. These markers will be used to identify each subpopulation in Aims #2 and 3. Aim #2 will use integrated anatomical/physiological experiments to determine if different interneuronal subpopulations exhibit distinct electrophysiological characteristics. In addition, ion channels responsible for some of these electrophysiological features will be localized using immunohistochemical techniques. Aim #3 will analyze the innervation of ABL neuronal subpopulations by dopaminergic, noradrenergic, and serotonergic afferents. It will also be determined using integrated anatomical-physiological/pharmacological methods if particular interneuronal subpopulations exhibit specific serotonin receptors. Aim #4 will analyze the innervation of ABL intemeuronal subpopulations by cholinergic axons and determine which interneurons express nicotinic versus muscarinic cholinergic receptors. Additional anatomical studies in rodents will test the hypothesis that the ABL, like the neocortex and hippocampus, contains subsets of GABAergic neurons that receive inputs from, and provide outputs to, the GABAergic projection neurons of the basal forebrain. These proposed studies include the first comprehensive analysis of the electrophysiological properties of identified ABL interneuronal subpopulations in both rodent and primate brain slices. In addition, the modulation of key electrophysiological properties in these neurons by serotonin and serotonergic drugs will be investigated. These studies will contribute to an understanding of inhibitory mechanisms in the ABL and should be critical for the development of novel pharmacological treatments to modulate the activity of the ABL in epilepsy and psychiatric disorders.