Intrinsic Properties of Cortical Layer 3 Pyramidal Cells in Monkeys

视觉工作记忆和注意力依赖于顶叶后叶之间的协调神经活动 大脑皮质(PPC)和背外侧前额叶皮质(DLPFC)。这两个区域通过投影直接相连。 来自第3层锥体细胞(PC)，这些细胞被预测为调节其功能连接(项目4)。 因此，提供这些投射的神经元中的细胞自主异常被认为是 精神分裂症患者PPC和DLPFC之间的功能连接受损(项目5)，导致 WM和注意。这一中心假设的一个关键要素是第3层PC的区域特定属性 这些神经元的分子(投射)和形态(投射2)病理的严重程度中等 在精神分裂症中；具体地说，DLPFC的第3层PC的病理被预测比在 PPC，因此预测从DLPFC到PPC的投影比来自PPC的投影更受损害- To-DLPFC(项目5)。该项目是所有第3层PC的项目1和2研究之间的重要桥梁 在人类PPC和DLPFC以及项目4中，专注于PPC和DLPFC之间的层3连接的研究 在猴子中的DLPFC如下：Aim 1提供了我们的翻译策略的关键评估，以测试 中心假说。首先，它测试了第三层PC基因表达的地区差异 人的PPC和DLPFC在猴子中是保守的。第二，通过专注于第3层PC， 互连PPC和DLPFC，它提供了对原产地占比的想法的稳健测试 通过控制其他已知与基因表达差异相关的因素来实现基因表达的差异 PC的某些分子特征或树枝状形态。因此，Aim 1提供了从Project的关键过渡 对所有第3层PC(目前不能基于它们的子集)在人类中进行的1和2项研究 主轴突投射)对猴子PPC和DLPFC相互连接的子集的研究。这些 基因表达的区域定义的差异被预测与 提供细胞的第3层PC的形态(目标2)和神经生理(目标3)特性 项目4中研究的猴子PPC和DLPFC之间功能连接的基础。 相关性(请参阅说明)： 这个项目将让我们了解注意力和工作记忆的神经回路基础 通过使用非人类灵长类动物模型系统来确定精神分裂症的损害， 在细胞类型、局部回路和区域间连接的水平上的特异性，关键属性 在人类受试者的功能和行为水平上研究了相同的神经回路。

Visual working memory and attention depend on coordinated neural activity between the posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (DLPFC). These two regions are directly linked by projections from layer 3 pyramidal cells (PCs) that are predicted to mediate their functional connectivity (Project 4). Consequently, cell-autonomous abnormalities in the neurons furnishing these projections are posited to impair functional connectivity between PPC and DLPFC in schizophrenia (Project 5), leading to deficits in WM and attention. A key element ofthis Central Hypothesis is that region-specific properties of layer 3 PCs moderate the severity of the molecular (Projecti) and morphological (Project 2) pathology of these neurons in schizophrenia; specifically, the pathology of layer 3 PCs is predicted to be more severe in DLPFC than in PPC, and thus the projections from DLPFC-to-PPC are predicted to be more impaired than those from PPC- to-DLPFC (Project 5). This project serves as a critical bridge between Project 1&2 studies of all layer 3 PCs in human PPC and DLPFC and the Project 4 studies that focus on the layer 3 connections between PPC and DLPFC in monkeys as follows: Aim 1 provides key assessments of our translational strategy for testing the Central Hypothesis. First, it tests the idea that regional differences in layer 3 PC gene expression between human PPC and DLPFC are conserved in monkeys. Second, by focusing on the layer 3 PCs that interconnect PPC and DLPFC, it provides a robust test of the idea that region of origin accounts for differences in gene expression by controlling for other factors known to be associated with differences in certain molecular features or dendritic morphology of PCs. Thus, Aim 1 provides a key transition from Project 1&2 studies in humans of all layer 3 PCs (which cannot currently be divided into subsets based on their principal axon projection) to studies of the subset that interconnect PPC and DLPFC in monkeys. These region-defined differences in gene expression are predicted to be associated with differences in morphological (Aim 2), and neurophysiological (Aim 3) properties of layer 3 PCs that provide the cellular basis for the functional connectivity between monkey PPC and DLPFC studied in Project 4. RELEVANCE (See instructions): This project will inform our understanding ofthe neural circuitry basis for attention and working memory impairments in schizophrenia through the use of a non-human primate model system to determine, with specificity at the levels of cell types, local circuits and inter-regional connections, the critical properties of the same neural circuitry studied at the functional and behavioral levels in human subjects.