Regional diversity of cortical white matter neurons in adult and infant rhesus monkey

成年和幼年恒河猴皮质白质神经元的区域多样性

• 批准号: 8939205
• 负责人: Kathleen Rockland
• 金额: $ 23.92万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-24 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8939205
• 关键词: 1 year old; Address; Adult; Age; Agreement; Anterior; Apoptosis; Architecture; Area; Auditory; Blood Vessels; Brain; Brain Pathology; Calcium-Binding Proteins; Cell Count; Cells; Communication; Data; Development; Disease model; Embryo; Experimental Designs; Goals; Histologic; Human; Imagery; Immunohistochemistry; In Vitro; Infant; Investigation; Label; Lateral Geniculate Body; Longevity; Macaca; Macaca mulatta; Modeling; Molecular; Monkeys; Motor; Mus; NADPH Dehydrogenase; Neonatal; Neuronal Plasticity; Neurons; Occipital lobe; Parietal Lobe; Patients; Perinatal; Population; Prefrontal Cortex; Primates; Process; Regulation; Reporting; Rodent; Role; Sampling; Schizophrenia; Slice; Symptoms; Temporal Lobe; The Sun; Tissues; Vasodilation; Visual; behavior test; caspase-3; cell type; cholinergic; cingulate cortex; cognitive reserve; density; excitatory neuron; falls; frontal lobe; gray matter; hemodynamics; inhibitory neuron; interest; nervous system disorder; neurochemistry; neuron development; neuropeptide Y; nonhuman primate; postsynaptic; public health relevance; regional difference; species difference; success; white matter

 DESCRIPTION (provided by applicant): White matter (WM) neurons are phylogenetically conserved; and in primates and other species with large gyrencephalic brains, substantial numbers of WM neurons persist beyond early development. These are neurochemically and morphologically heterogeneous. During development, these neurons are known to have essential roles in the establishment of both thalamocortical and corticocortical circuitry, and are implicated in gyral formation (Suarez-Sola et al., 2009; Kanold and Luhmann, 2010; Zilles et al., 2013; Sun and Hevner, 2014). In the adult, very little is known about these neurons, beyond the fact that at least some of these are incorporated into cortical circuitry. An important role in vascular regulation is strongly suggested for a contingent of NOS-positive WM neurons (Barbaresi et al., 2014). Further, WM neurons have attracted interest since the density of superficial WM neurons is increased in brains of some schizophrenic subjects as compared with controls (Connor et al., 2011; Yang et al., 2011). Increased density of WM neurons is also reported in the brains of autistic subjects (McFadden and Minshew, 2013). The present proposal is motivated by the hypothesis that WM neurons remain functionally important in the adult and that a nonhuman primate model will offer productive opportunities for further cellular, molecular, and circuit-level investigations. A monkey model is needed because of the greater accessibility of monkeys, as opposed to humans, to experimental manipulations, and because of the many developmental and circuitry differences between primates and rodents (Judas et al., 2010b). Key parts of the experimental design are 1) a systematic quantitative analysis of the superficial and deep WM populations in the adult rhesus monkey, sampled across different cortical regions and scored in terms of excitatory and inhibitory subpopulations, and 2) a comparable analysis in the perinatal and infant monkey (<12 months), to determine region- and cell-type differences in the numerical fall-off of WM neurons. Visualization of WM subpopulations will be by immunohistochemistry for NeuN and other standard cell type markers, in histologically sectioned brains. Success will be defined as identifying that region specific differences occur in both the adult and infant brain, as is predicted by region specific differences already reported in the human brain (Garcia-Marin et al., 2010). Anticipated next steps, in an eventual R01, would be to address network connectivity and postsynaptic targets of WM subpopulations, and to investigate anatomical differences in the WM populations across the lifespan and in monkey models of disease and other conditions.

 描述（由申请人提供）：白色物质（WM）神经元在遗传学上是保守的;在灵长类动物和其他具有大脑回的物种中，大量WM神经元在早期发育后仍然存在。它们在神经化学和形态学上是异质的。在发育过程中，已知这些神经元在丘脑皮层和皮质皮层回路的建立中具有重要作用，并且在发育过程中， 与脑回形成有关（Suarez-Sola等，2009; Kanold和Luhmann，2010; Zilles等人，2013; Sun和Hevner，2014）。在成年人中，人们对这些神经元知之甚少，除了至少其中一些被纳入皮层回路之外。强烈建议NOS阳性WM神经元在血管调节中发挥重要作用（Barbaresi等人，2014年）。此外，由于与对照相比，在一些精神分裂症受试者的脑中，表面WM神经元的密度增加，因此WM神经元引起了兴趣（康纳等人，2011年; Yang等人，2011年）。在自闭症受试者的大脑中也报告了WM神经元密度增加（McFadden和Minshew，2013）。本建议的动机是假设WM神经元在成人中仍然具有重要的功能，并且非人灵长类动物模型将为进一步的细胞，分子和电路水平的研究提供富有成效的机会。需要猴模型，因为与人类相比，猴更容易进行实验操作，并且因为灵长类动物和啮齿类动物之间的许多发育和电路差异（Judas et al.，2010年b）。实验设计的关键部分是：1）对成年恒河猴的浅层和深层WM群进行系统定量分析，在不同皮质区域进行采样，并根据兴奋性和抑制性亚群进行评分; 2）对围产期和婴儿猴（<12个月）进行可比分析，以确定WM神经元数量下降的区域和细胞类型差异。WM亚群的可视化将通过组织切片脑中NeuN和其他标准细胞类型标志物的免疫组织化学进行。成功将被定义为识别出成人和婴儿大脑中发生的区域特异性差异，正如已经报道的区域特异性差异所预测的那样。 人脑（加西亚-马林等人，2010年）。在最终的R 01中，预期的下一步将是解决WM亚群的网络连接和突触后靶点，并研究WM群体在整个生命周期以及疾病和其他条件的猴子模型中的解剖差异。