SYNAPTIC PHARMACOLOGY OF LIMBIC/STRIATAL CONNECTIONS

描述(改编自申请人的摘要)：较长期 本项目的目标是研究两个神经元之间的突触相互作用。 前脑的主要组成部分：边缘皮质和纹状体。 具体目标是建立详细的生理和 边缘皮质向大脑皮质投射的药理学特性 细胞水平上的纹状体。研究将集中在一个特定的方面 通路--从内嗅觉皮质到NAC的投射。研究 将在体内大鼠体内使用细胞内制剂进行 辣根单细胞的记录、细胞内标记 过氧化物酶(HRP)和多管离子导入。合并后的 这些先进程序的应用将用于建立 关于神经元相互作用的详细信息。因此，目前的研究是 旨在获得生理、形态和 关于这些神经元突触关系的神经药理学数据 区域，包括有关其电路属性和 传送器物质。 NAC是腹侧纹状体的重要组成部分。这个 内嗅皮层是海马体结构的关键结构， 许多海马体的输入和输出都是通过它进行的。直接 已经证实了从内嗅皮层到NAC的投射 通过现代神经解剖追踪技术。然而尽管如此， 紧密的、单向的神经解剖关系，申请人声称 目前还没有可发表的细胞生理或药理学数据 到目前为止，在这一研究领域即将开展的工作。本项目计划 重点研究以下几个问题：(1)突触 从内嗅觉皮质到 生理和形态定义的NAC神经元；(2) 谷氨酸受体亚型介导NAC的兴奋性反应 神经元对来自内嗅皮层的突触输入；(3)哪个伽马 氨基丁酸(GABA)能受体亚型介导继发性 纹状体神经元对内嗅觉突触输入的抑制作用 皮层；以及(4)不同区域对NAC的兴奋性传入 边缘皮质在单个NAC神经元水平上相互作用。 NAC涉嫌滥用药物和精神疾病，包括 躁狂症和精神分裂症。也有一些提示性的证据表明 内嗅皮层可能通过以下方式参与精神分裂症 精神分裂症患者脑组织病理改变的观察 病人。因此，当前项目的更广泛意义 可能与理解 边缘皮质和纹状体在精神病性症状产生中的作用 药物治疗的副作用。

DESCRIPTION (Adapted from applicant's abstract): The longer-term objective of this project is to study the synaptic interaction of two major components of the forebrain: the limbic cortex and the striatum. The specific aims are to establish in detail the physiological and pharmacological properties of projections from limbic cortex to the striatum at a cellular level. Research will focus on one particular pathway -- projections from the entorhinal cortex to the NAc. Research will be performed in the in vivo rat preparation using intracellular recording, intracellular labeling of single cells with horseradish peroxidase (HRP), and multibarrel iontophoresis. The combined application of these advanced procedures will be used to establish details about neuronal interactions. Hence, the present studies are designed to obtain physiological, morphological, and neuropharmacological data regarding the synaptic relationship of these areas, including information about their circuit properties and transmitter substances. The NAc is an important component of the ventral striatum. The entorhinal cortex is a key structure of the hippocampal formation, and much hippocampal input and output is funnelled through it. Direct projections from the entorhinal cortex to the NAc have been demonstrated by modern neuroanatomical tracing techniques. However, despite this close, one-way neuroanatomical relationship, the applicant claims that no publishable cellular physiological or pharmacological data have been forthcoming in this research area to date. The present project plans to focus on the following questions concerning: (1) the synaptic organization of projections from the entorhinal cortex to physiologically and morphologically defined NAc neurons; (2) which glutamatergic receptor subtypes mediate excitatory responses of NAc neurons to synaptic inputs from the entorhinal cortex; (3) which gamma aminobutyric acid (GABA)ergic receptor subtypes mediate the secondary inhibitor of striatal neurons to synaptic inputs from the entorhinal cortex; and (4) how excitatory inputs to the NAc from distinct regions of limbic cortex interact at the level of single NAc neurons. The NAc has been implicated in drug abuse and mental illness, including mania and schizophrenia. There is also some suggestive evidence that the entorhinal cortex may be involved in schizophrenia by virtue of histopathological abnormalities observed in the brains of schizophrenic patients. Accordingly, the broader significance of the current project may be its possible relevance to understanding interactions between the limbic cortex and striatum in the production of psychotic symptoms and drug treatment side-effects.