Serotonergic regulation of sensorimotor gating in mice

小鼠感觉运动门控的血清素调节

• 批准号: 6690887
• 负责人: DAVID C AIREY
• 金额: $ 4.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6690887
• 关键词: G protein; autoradiography; behavioral /social science research tag; biological signal transduction; gene expression; genetic polymorphism; laboratory mouse; neural inhibition; neuropsychology; phenotype; polymerase chain reaction; postdoctoral investigator; sensorimotor system; serotonin receptor

DESCRIPTION (provided by applicant): Animals are effectively used to model prepulse inhibition, the ability of a detectable stimulus to inhibit or gate response to a secondary startling stimulus. Deficits in prepulse inhibition are seen in persons with schizophrenia, their relatives, and persons with schizotypal disorder. This application proposes to analyze the role of variation in two genes, Htr1a and Htr1b, and their products, the G-protein coupled serotonin receptors 5-HT1A and 5-HT1B, in sensorimotor gating processes in mice. Previous analyses of pharmacologic effects and knockout mice implicate these genes and receptors in regulating prepulse inhibiton, but it is unknown if or how they might play a role in determining differences between individuals or isogenic strains. Twenty genetically and phenotypically diverse inbred mouse strains will be surveyed for variation at three levels, (i) genetic sequence, (ii) brain receptor distribution, and (iii) agonist actions on prepulse inhibition. The hypothesis that genetic variation in Htr1a and Htr1b influences sensorimotor gating processes will be evaluated by direct association of strain haplotype and behavioral phenotype. Variation in the distribution of functional receptors in the brain will be tested as a neural phenotype mediating genetic and behavioral differences.

描述（由申请人提供）：动物有效地用于建模预硫抑制作用，可检测到的刺激抑制或栅极反应对次要惊人刺激的能力。在精神分裂症，亲戚和精神分裂症患者的人中看到了预硫次抑制的缺陷。该应用建议分析两个基因HTR1A和HTR1B及其产物的变异作用，即G蛋白偶联的5-羟色胺受体5-HT1A和5-HT1B在小鼠的感觉运动控件中。先前对药理学作用和基因敲除小鼠的分析暗示了这些基因和受体在调节预硫代抑制剂方面，但未知它们是否或如何在确定个体或同源性菌株之间的差异中发挥作用。将调查二十种遗传和表型多样的近交小鼠菌株，以在三个级别的变异，（i）遗传序列，（ii）脑受体分布和（iii）激动剂对预硫抑制作用的作用。 HTR1A和HTR1B的遗传变异影响感觉运动门控过程的假设将通过菌株单倍型和行为表型的直接关联来评估。大脑功能受体分布的变化将作为介导遗传和行为差异的神经表型测试。