SENSORY GATING PHYSIOLOGY IN LIMBIC FOREBRAIN

边缘前脑的感觉门控生理学

• 批准号: 3781942
• 负责人: GREGORY M ROSE
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3781942
• 关键词: afferent nerve; auditory pathways; auditory stimulus; brain electrical activity; brain mapping; disease /disorder model; electrophysiology; evoked potentials; experimental brain lesion; hippocampus; inhibitor /antagonist; laboratory rat; limbic system; neural information processing; neurobiology; neurotoxins; neurotransmitters; nucleic acid repetitive sequence; prosencephalon; schizophrenia; sensory mechanism; stimulant /agonist

Deficits in auditory processing are a characteristic of schizophrenia. These have been formally demonstrated using a sensory gating paradigm in which surface auditory evoked potentials (AEPs) are measured in response to the presentation of closely paired clicks. Schizophrenics, unlike normal controls, show little or no inhibitory gating of a midlatency wave, P50, to the second click. The synaptic pathways and neurobiological mechanisms which are responsible for normal sensory gating, or the deficit seen in schizophrenia, are not known. Further, these circuits and mechanisms cannot be investigated in human subjects, due to the invasive nature of the anatomical and physiological technique involved. While there is no animal model of schizophrenia, there is a significant amount of evidence that the hippocampus is a site of pathology in this disease. We also have preliminary evidence for a hippocampal AEP in rats, N50, which has many features in common with human P50. The purpose of this project is to determine how auditory input reaches the hippocampus and how it is gated there. The results of this work will not definitively demonstrate which neuronal mechanisms are responsible for the gating of human P50, but they will indicate possible directions for further investigation in other projects in the Center. In collaboration with Project 4, we will explore the electrophysiology of sensory gating in nonhuman primates to validate our findings in a more "advanced" brain. In collaboration with Project 5, we will isolate relevant circuits in intraocular transplants made from fetal rat tissue. This work will guide subsequent experiments in Project 5 which will involve transplantation of human fetal tissues.

听觉处理的缺陷是 精神分裂症。 这些已通过 感官门控范式在其中唤起表面听觉 电势（AEP）是根据表现的 紧密配对的点击。 精神分裂症患者，与正常对照不同， 几乎没有或没有抑制性的抑制性门p50 p50 第二次点击。 突触途径和神经生物学 负责正常感觉门控的机制或 精神分裂症中看到的赤字尚不清楚。 此外，这些 电路和机制不能在人类受试者中进行研究， 由于解剖学和生理的侵入性 涉及的技术。 虽然没有动物模型的 精神分裂症，有大量证据表明 海马是该疾病的病理部位。 我们也有 N50大鼠海马AEP的初步证据 与人P50有许多共同的功能。 这个目的 项目将确定听觉输入如何达到 海马及其在那里的门控。 这项工作的结果 不会明确证明哪些神经元机制是 负责人P50的门控，但它们将表明 可能在其他项目中进行进一步调查的可能指示 在中心。 与项目4合作，我们将探索 非人类灵长类动物中感觉门控的电生理学 在更“高级”的大脑中验证我们的发现。 在 与项目5合作，我们将隔离相关电路 在由胎儿大鼠组织制成的眼内移植中。 这项工作 将指导项目5中的后续实验，该实验将涉及 人胎儿组织的移植。