LOCAL INTERACTIONS AMONG HIPPOCAMPAL NEURONS

海马神经元之间的局部相互作用

• 批准号: 2858102
• 负责人: PHILIP A SCHWARTZKROIN
• 金额: $ 29.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2858102
• 关键词: adrenalectomy; calcium flux; experimental brain lesion; gene induction /repression; glutamate receptor; glutamates; granule cell; hippocampus; immunocytochemistry; kainate; laboratory rat; long term potentiation; mossy fiber; neural information processing; neural inhibition; neural plasticity; neuroanatomy; neuropharmacology; neuroprotectants; neurotransmitter transport; neurotrophic factors; pyramidal cells; steroid hormone

The hippocampus of the mammalian brain, and particularly the dentate regions with its various inter-connections, are now recognized as playing key roles in both normal and pathological brain functions. The dentate gyrus, as the primary "relay" for cortical input to the hippocampus, processes information critical to complex behaviors such as learning and memory. The activity and integrity of dentate neuronal populations may also set the level of excitability in the limbic system; maximal activation of dentate neurons facilitates spread of seizure activity, and dentate cell loss and/or axonal reconnectivity has been implicated in various animal models of epileptogenesis as well as in human epilepsy. Finally, studies of the connectivity and receptor populations of hippocampus have begun to implicate this limbic structure in a variety of issues relevant to affective disorders. Given these roles, it seems particularly important to elucidate the local connections of the hippocampal/dentate region and to examine its responses to modulatory substances. Over the past several years, we have attempted to characterize the properties and connectivities of some of the hippocampal interneuron populations. We propose to continue that analysis, with a particular focus on the pathways of interaction between the dentate and pyramidal cell regions. Our work has suggested that far from being a simple relay between entorhinal cortex and Ammon's horn, the dentate gurus has complex circuitry and a large number of cell types with unique characteristics. These observations add to studies from other laboratories which show the dentate gurus to be one among the "hot spots" in the brain for receptors to potential modulatory substances. Changes in circulating steroid hormone levels has been shown to affect the integrity of the granule cells and their targets in CA3 neurotrophic factors and their receptors have now been found in these neurons; and mRNAs for a variety of factors can be altered as a function of electrical activities. Despite these findings, relatively little is known about how neuromodulatory substances, such as hormones or neurotrophins, affect dentate function. We propose to continue our elucidation of hippocampal circuitry, and to examine the direct affects of steroid hormones, neurotrophins and other potential modulatory substances on granule cells, and on granule cell synaptic transmission to dentate hilar and CA3 pyramidal cells. We will focus on circuits and drug actions that are likely to be significant for tissue plasticity, excitability, and viability. Electrophysiological recording and optical imaging, complimented by electron microscopy and immunocytochemistry, will be employed in these attempts to shed some light on the pathways of information transfer through the dentate, and on the processes by which that transfer can be modulated.

哺乳动物大脑的海马体，特别是齿状回 地区与其各种相互联系，现在被认为是发挥 在正常和病理大脑功能中的关键作用。齿状 脑回作为皮质输入到海马体的主要“中继”， 处理对复杂行为至关重要的信息，如学习和 记忆齿状核神经元群的活性和完整性可能 也设置了边缘系统的兴奋性水平;最大 齿状神经元的激活促进癫痫活动的扩散， 齿状细胞丢失和/或轴突重新连接已经涉及到 各种癫痫发生的动物模型以及人类癫痫。 最后，研究的连接和受体群体的 海马体已经开始将这种边缘系统结构与各种 与情感障碍有关的问题。考虑到这些角色， 特别重要的是要阐明当地的联系， 海马/齿状回区，并检查其对调节 物质.在过去的几年里，我们试图描述 一些海马中间神经元的特性和连通性 人口。我们提议继续进行这一分析， 齿状回和锥体细胞之间相互作用的途径 地区我们的研究表明， 内嗅皮层和阿蒙角，齿状古鲁有复杂的 电路和大量具有独特特性的细胞类型。 这些观察结果补充了其他实验室的研究，这些研究表明， 齿状大师将成为大脑中受体的“热点”之一 潜在的调节物质。循环类固醇激素的变化 水平已被证明会影响颗粒细胞的完整性， 他们的目标是CA 3神经营养因子及其受体， 在这些神经元中发现;各种因子的mRNA可以被 作为电活动的功能而改变。尽管有这些发现， 关于神经调节物质，如 激素或神经营养素，影响齿状功能。我们建议继续 我们的海马电路的阐明，并检查直接 类固醇激素、神经营养素和其他潜在的调节因子的影响 颗粒细胞上的物质，以及颗粒细胞突触传递， 齿状门区和CA 3区锥体细胞。我们将专注于电路和药物 可能对组织可塑性有重要意义的行为， 兴奋性和生存能力。电生理记录和光学 成像，辅以电子显微镜和免疫细胞化学， 在这些尝试中使用，以揭示一些途径， 信息通过齿状传递，以及 这种转移是可以调节的。