SYNAPTIC PHARMACOLOGY OF LIMBIC/STRIATAL CONNECTIONS

描述（改编自申请人摘要）：长期 该项目的目的是研究两个突触的相互作用， 前脑的主要组成部分：边缘皮层和纹状体。 具体目标是详细建立生理和 从边缘皮层到大脑皮层的投射的药理学特性 在细胞水平上。 研究将集中在一个特定的 通路--从内嗅皮层到NAc的投射。 研究 将在体内大鼠制备中使用细胞内 记录，辣根单细胞的细胞内标记 过氧化物酶（HRP）和多筒离子电渗法。 将合并的 应用这些先进的程序将用于建立 神经元相互作用的细节因此，目前的研究 旨在获得生理、形态和 神经药理学数据关于这些突触的关系 区域，包括有关其回路属性的信息， 发射器物质。 NAc是腹侧纹状体的重要组成部分。 的 内嗅皮层是海马结构的关键结构， 许多海马体的输入和输出都是通过它进行的。 内嗅皮层到NAc的投射已经被证实 通过现代神经解剖追踪技术。 不过尽管如此 申请人声称，这种密切的单向神经解剖关系 还没有可靠的细胞生理学或药理学数据 在这个研究领域，到目前为止。 本项目计划 重点讨论以下问题：（1）突触 从内嗅皮层到 生理学和形态学定义的NAc神经元;（2） 多巴胺能受体亚型介导NAc的兴奋性反应 神经元的突触输入从内嗅皮层;（3）γ 氨基丁酸（GABA）能受体亚型介导继发性 抑制纹状体神经元对来自内嗅的突触输入的抑制剂 皮质;（4）兴奋性输入如何从不同的区域到NAc 在单个NAc神经元的水平上相互作用。 NAc涉嫌滥用药物和精神疾病，包括 躁狂症和精神分裂症。 还有一些暗示性的证据表明， 内嗅皮层可能与精神分裂症有关， 精神分裂症患者脑组织病理学改变 患者 因此，当前项目的更广泛意义 可能是它与理解 边缘皮层和纹状体在精神病症状的产生中的作用， 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.