STRUCTURE/FUNCTION OF SUBCORTICAL WHITE MATTER NEURONS

皮质下白质(SCWM)神经元是灵长类新皮质的常见特征，在人类中大量存在。这些细胞被认为是亚板的残留物，可能在新皮质发育过程中起到了指南针的作用。SCWM神经元在成人中的功能尚不清楚，但由于它们在出生后早期具有广泛的轴突，它们可能会影响成年后皮质大片区域的活动。尽管其重要性尚不清楚，但在各种神经疾病中，SCWM神经元的数量也有所增加，包括精神分裂症、各种形式的癫痫，或许还有阿尔茨海默病。因此，检查这些细胞的突触组织和生理学对于全面了解正常和病理的皮质功能是很重要的。这个项目的目标是测试SCWM神经元整合到新皮质回路中的假设。这项研究特别适合使用人类组织进行，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身上进行的研究可能不适用于人类；2)在非人类灵长类动物身上进行此类研究的成本将是高昂的。手术切除治疗顽固性癫痫患者的组织是常规可用的。这些切除通常包括与癫痫发作有关的区域以及这些区域附近相对正常的组织。我们将结合解剖学和生理学技术研究SCWM神经元是否整合到神经元回路中。如果这一假设成立，应该有证据表明这些细胞和新皮质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，以检查这些细胞的胞体和近端树突上是否存在突触，这些突触来自皮质。此外，这些细胞的突触输出将通过检查充满生物细胞素的细胞的轴突来检测。SCWM细胞的突触靶点将通过双标记研究来确定。生理学研究将通过记录视觉识别的SCWM神经元来进行。除了这些细胞的生理学特征外，我们还将检查这些细胞是否从新皮质接受自发或诱发的突触活动，以及可能的递质(S)。所有生理学研究的细胞都将被标记生物细胞素，以允许我们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质功能中可能扮演的角色的第一个信息。考虑到这些细胞可能参与了各种神经系统疾病，因此对这些细胞进行完整的描述是至关重要的。

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.