Serotonergic regulation of sensorimotor gating in mice

描述（由申请人提供）：动物被有效地用于模拟脉冲前抑制，即可检测到的刺激抑制或抑制对次级惊吓刺激的反应的能力。脉搏前抑制缺陷见于精神分裂症患者、其亲属和精神分裂型障碍患者。本申请旨在分析Htr1a和Htr1b两个基因及其产物g蛋白偶联5-HT1A和5-HT1B在小鼠感觉运动门控过程中的作用。先前对药理学效应和基因敲除小鼠的分析表明，这些基因和受体参与调节脉冲前抑制，但尚不清楚它们是否或如何在决定个体或等基因菌株之间的差异中发挥作用。20个遗传和表型不同的近交系小鼠将在三个水平上进行变异调查，(i)基因序列，（ii）脑受体分布，（iii）激动剂对脉冲前抑制的作用。Htr1a和Htr1b基因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。大脑中功能受体分布的变化将作为神经表型介导遗传和行为差异进行测试。

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.