GABAergic Modulation of Pulvinar Projection Cells

枕投射细胞的 GABA 能调节

• 批准号: 7911355
• 负责人: Jonathan David Day-Brown
• 金额: $ 2.87万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911355
• 关键词: Affect; Amygdaloid structure; Attention; Bicuculline; Binding; Brain; Butyric Acids; Cell Nucleus; Cells; Confocal Microscopy; Controlled Study; Corpus striatum structure; Disease; Electron Microscopy; Exhibits; Facial Expression; Goals; Human; Image; Lesion; Light; Motion Perception; Neurons; Neurotransmitters; Pathway interactions; Patients; Physiological; Play; Primates; Property; Prosimii; Pulvinar structure; Role; Schizophrenia; Signal Transduction; Symptoms; Synapses; Tupaia; Tupaiidae; Visual; Visual Motion; Visual attention; cell type; experience; immunocytochemistry; nerve supply; prototype; public health relevance; receptor; research study; response; visual stimulus

DESCRIPTION (provided by applicant): The function of the pulvinar nucleus is largely unexplored, although it is thought to play a key role in visual attention and visual motion perception. Recently the pulvinar nucleus has gained attention because it has been found to be significantly smaller in schizophrenic brains when compared to controls, and studies of patients with restricted lesions of the pulvinar nucleus exhibit some of the same visual deficits experienced by schizophrenic patients. Therefore further study of the pulvinar nucleus could shed light on brain circuits affected by schizophrenia. The proposed experiments focus on the physiological response properties and synaptic organization of the pulvinar nucleus and its projections to the striatum and amygdala, with the goal of elucidating how these circuits are modulated by the neurotransmitter gamma amino butyric acid (GABA). Anatomical experiments will determine whether separate cell types project to the striatum and amygdala using tract tracing and confocal microscopy. Immunocytochemistry and electron microscopy will be used to compare the GABAergic innervation of pulvinar neurons that project to the striatum or amygdala, and physiological experiments will compare the responses of these two cell types to moving visual stimuli in the presence or absence of the GABA receptor antagonist bicuculline. The proposed studies will use the tree shrew (Tupaia belangeri), which is considered to represent a prototype of early prosimian primates. Therefore our results should be easily related to primate brain organization, and could shed light on human disorders, such as schizophrenia. PUBLIC HEALTH RELEVANCE: Studies of patients with restricted pulvinar lesions have revealed a wide array of visual deficits, including the diminished ability to filter distracting signals, difficulty in binding image features, or difficulty in recognizing facial expressions. Because schizophrenic patients exhibit similar deficits, and the pulvinar nucleus of schizophrenic patients has been shown to be smaller than that of control subjects, our proposed studies could shed light on potential pulvinar pathways involved in symptoms of this disease.

描述（由申请人提供）：枕核的功能在很大程度上尚未探索，尽管它被认为在视觉注意和视觉运动感知中起关键作用。最近，枕核引起了人们的注意，因为它已被发现是显着较小的精神分裂症患者的大脑相比，对照组，和患者的研究与限制性损害的枕核表现出一些相同的视觉缺陷的精神分裂症患者经历。因此，对枕核的进一步研究可能有助于阐明精神分裂症影响的脑回路。拟议的实验集中在枕核的生理反应特性和突触组织及其对纹状体和杏仁核的投射，目的是阐明这些电路是如何由神经递质γ-氨基丁酸（GABA）调制的。解剖学实验将确定是否单独的细胞类型的项目纹状体和杏仁核使用束跟踪和共聚焦显微镜。免疫细胞化学和电子显微镜将用于比较投射到纹状体或杏仁核的枕神经元的GABA能神经支配，生理学实验将比较这两种细胞类型在存在或不存在GABA受体拮抗剂荷包牡丹碱的情况下对移动视觉刺激的反应。拟议中的研究将使用树鼩（Tupaia belangeri），它被认为是早期原猴亚目灵长类动物的原型。因此，我们的研究结果应该很容易与灵长类动物的大脑组织联系起来，并可能揭示人类疾病，如精神分裂症。 公共卫生相关性：对限制性枕病变患者的研究显示了广泛的视觉缺陷，包括过滤干扰信号的能力下降，难以结合图像特征或难以识别面部表情。由于精神分裂症患者表现出类似的缺陷，和枕核的精神分裂症患者已被证明是小于对照组，我们提出的研究可能揭示了潜在的枕途径参与这种疾病的症状。