ANIMAL MODELS OF SENSORY GATING DEFECTS

感觉门控缺陷的动物模型

• 批准号: 6243056
• 负责人: GREGORY M ROSE
• 金额: $ 21.21万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243056
• 关键词: auditory feedback; auditory stimulus; biological models; brain electrical activity; bungarotoxins; catecholamines; evoked potentials; experimental brain lesion; genetic strain; hippocampus; immunocytochemistry; in situ hybridization; inbreeding; laboratory mouse; laboratory rat; neural transmission; neuroanatomy; neuropharmacology; nicotine; nicotinic receptors; perception disorder; reticular formation; schizophrenia; sensory mechanism; synapses

Deficits in sensory processing are a hallmark of schizophrenia. These deficits can be evaluated by surface recording of auditory evoked potential (AEPs) elicited in response to closely paired click stimuli. Normal individuals have a reduced, or gated, middle latency (P50) response to the second click as compared to the first, while schizophrenics are not able to gate their responses to the same stimuli. Fill delineation of the synaptic pathways and neurobiological mechanisms of sensory gating cannot be investigated in humans due to the invasive nature of the anatomical and physiological techniques involved. Although there is no animal model of schizophrenia available,, a model of sensory gating has been developed. Rats (both anesthetized and awake) show gating of a middle latency AEP (N40), in response to paired clicks; administration of psychogenic agents (amphetamine, PCP) produces a schizophrenia-like response pattern. This model permits inquiry into the neuronal circuitry and neurochemical basis of sensory gating which may be of heuristic value in indicating future directions for human investigations in other projects in the Center. In this project, the animal model will be used to further several areas of investigation. Intrinsic interanimal variability in gating will be used to evaluate the relative roles of catecholaminergic and cholinergic neurotransmission in the regulation of gating. Since recent data have indicated a role for the cholinergic system in the regulation of sensory gating in both humans and rats, the specific contribution of forebrain cholinergic pathways to sensory gating will be evaluated. In addition, the neuronal circuitry responsible for the regulation of septal modulation of gating will be identified through PHA-L tracing and immunohistochemical techniques. Finally, the specific role of the alpha-bungarotoxin binding site in gating will be assessed through acute hippocampal recordings of mice selectively bred for differing numbers of these binding sites.

感觉处理的缺陷是精神分裂症的标志。 这些 可以通过唤起听觉的表面记录来评估缺陷 电势（AEP）响应紧密配对的点击刺激而引起。 普通人的中等潜伏期降低或门控（P50） 与第一个相比，对第二次点击的响应，而 精神分裂症患者无法对同一刺激的反应进行反应。 填充突触途径和神经生物学机制的描述 由于侵入性，无法在人类中调查感官门控的 所涉及的解剖学和生理技术的性质。 虽然 没有可用的精神分裂症动物模型，一种感觉模型 已经开发了门控。 大鼠（麻醉和清醒）表演 响应配对的点击，中等潜伏期AEP（N40）的门控； 施用心理剂（苯丙胺，PCP）会产生一种 精神分裂症样反应模式。 该模型允许查询 感觉门的神经元电路和神经化学基础 在指示人类未来的方向方面具有启发式价值 中心其他项目的调查。 在这个项目中， 动物模型将用于进一步的几个研究领域。 门控的固有互想变异将用于评估 儿茶酚胺能和胆碱能神经传递的相对作用在 门控的调节。 由于最近的数据表明了 两个人的感觉门控调节中的胆碱能系统 和大鼠，前脑胆碱能途径的具体贡献 感官门控将评估。 另外，神经元电路 负责对门控调节调节的调节将是 通过PHA-L追踪和免疫组织化学技术鉴定。 最后，alpha-bungarotoxin结合位点在 门控将通过小鼠的急性海马记录来评估 选择性地育出了这些结合位点的不同数量。