STRUCTURE/FUNCTION OF SUBCORTICAL WHITE MATTER NEURONS

皮层下白质神经元的结构/功能

• 批准号: 6187907
• 负责人: DENNIS D SPENCER
• 金额: $ 25.02万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187907
• 关键词: axon; biocytin; biopsy; brain cell; developmental neurobiology; electron microscopy; electrophysiology; epilepsy; extracellular; fluorescent dye /probe; human tissue; immunocytochemistry; infrared microscopy; neocortex; neuroanatomy; neurons; soma; synapses

Subcortical white matter (SCWM) neurons are a common feature in the primate neocortex and are present in large numbers in the human. These cells are believed to be the remnant of the subplate and may have served guidepost functions during neocortical development. The function of SCWM neurons in the adult is unknown, however because they have extensive axonal processes in early postnatal life, they may be able to affect the activity of large regions of cortex into adulthood. Although the significance is not yet known, there are also increased numbers of SCWM neurons in a variety of neurological diseases, including schizophrenia, forms of epilepsy and, perhaps, Alzheimer's disease. It is important, therefore, to examine the synaptic organization and physiology of these cells for a complete understanding of both normal and pathological cortical function. The goal of this project is to test the hypothesis that SCWM neurons are integrated into the neocortical circuitry. This study is uniquely suited to be carried out using human tissue for two reasons; 1) the density of SCWM neurons increases with the complexity of the organism, therefore studies carried out in animals such as rodents or cats may not be applicable to humans; 2) the costs of carrying out such a study in non-human primates would be prohibitive. Tissue from patients undergoing resection for the treatment of intractable epilepsy is routinely available. These resections typically include areas involved in seizure generation as well as relatively normal tissue adjacent to these areas. We will examine whether SCWM neurons are integrated into the neuronal circuitry using a combination of anatomical and physiological techniques. If this hypothesis is valid, there should be evidence for both synaptic inputs and outputs between these cells and the neocortex. Electron microscopic studies of this tissue will be performed to examine whether there are synapses onto the soma and proximal dendrites of these cells that arise from the cortex. In addition, the synaptic output of these cells will be assayed by examining the axonal arbors of biocytin- filled cells. The synaptic targets of SCWM cells will be identified using double labeling studies. Physiological studies will be performed by recording from visually identified SCWM neurons. In addition to characterizing these cells physiologically, we will examine whether these cells receive spontaneous or evoked synaptic activity from the neocortex and the possible transmitter(s) underlying any synaptic activity. All cells studied physiologically will be labeled with biocytin to allow us to verify the cell type and for use in the anatomical experiments. These studies will provide the first information on the possible role of these cells in the function of the adult neocortex. Given the possible involvement of these cells in a variety of neurological disorders, it is critical to characterize these cells completely.

皮质下白色物质（SCWM）神经元是灵长类动物新皮层的一个共同特征，在人类中大量存在。 这些细胞被认为是基板的残余，并可能在新皮层发育过程中起到路标的作用。 SCWM神经元在成人中的功能是未知的，然而，因为它们在出生后的早期具有广泛的轴突过程，它们可能能够影响成年后大面积皮质区域的活动。 虽然其意义尚不清楚，但在各种神经系统疾病中，包括精神分裂症，癫痫形式以及可能的阿尔茨海默病中，SCWM神经元的数量也有所增加。 因此，研究这些细胞的突触组织和生理学对于全面了解正常和病理性皮质功能是很重要的。这个项目的目标是测试的假设，SCWM神经元整合到新皮层电路。 这项研究特别适合使用人体组织进行，原因有两个：1）SCWM神经元的密度随着生物体的复杂性而增加，因此在啮齿动物或猫等动物中进行的研究可能不适用于人类; 2）在非人类灵长类动物中进行此类研究的成本将是高昂的。 接受切除术治疗顽固性癫痫的患者的组织是常规可用的。这些切除通常包括涉及癫痫发作的区域以及邻近这些区域的相对正常的组织。 我们将研究是否SCWM神经元整合到神经元回路使用解剖学和生理学技术相结合。 如果这一假设成立，那么就应该有证据表明这些细胞和新皮层之间存在突触输入和输出。 将对该组织进行电子显微镜研究，以检查是否有突触连接到这些细胞的索马和近端树突上，这些细胞起源于皮质。 此外，这些细胞的突触输出将通过检查充满生物胞素的细胞的轴突乔木来测定。 将使用双标记研究来鉴定SCWM细胞的突触靶点。 将通过记录视觉识别的SCWM神经元进行生理学研究。 除了从生理学上表征这些细胞外，我们还将检查这些细胞是否从新皮层接收自发或诱发的突触活动以及任何突触活动背后的可能递质。所有生理学研究的细胞都将用生物胞素标记，以使我们能够验证细胞类型并用于解剖学实验。 这些研究将提供有关这些细胞在成人新皮层功能中可能作用的第一个信息。 考虑到这些细胞可能参与各种神经系统疾病，完全表征这些细胞至关重要。