BEHAVIOR

行为

• 批准号: 3735383
• 负责人: VICTOR H DENENBERG
• 金额: --
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 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/3735383
• 关键词: association learning; autoimmune disorder; avoidance behavior; behavior test; biological models; brain disorders; cues; discrimination learning; genetic strain; handedness; immunodeficiency; laboratory mouse; learning; learning disorders; memory; neuropsychology; performance; problem solving; psychoneuroimmunology; psychopharmacology; reading disorder

Two autoimmune mouse strains, NZB and BXSB, have 40-48% incidence of cortical ectopias, and associated behavioral deficits. Research over the past five years has found that (1) left and right pawed ectopic mice differ on spatial and non-spatial associative learning tasks; (2) mice with autoimmunity have markedly depressed avoidance learning scores; (3) exposure to an enriched environment during early development facilitates learning in non-ectopic and ectopic mice, with some evidence that the non- ectopics profit more from the experience; and (4) the nature of the uterine environment (autoimmune or not) significantly influences the degree of autoimmunity of the offspring and subsequent avoidance learning. this proposal builds upon these findings and has the following purposes: (1) develop a set of higher-order learning tasks to more sharply distinguish those with biological anomalies (autoimmunity and ectopias); (2) investigate procedures for facilitating learning, including (i) extending early enrichment experiences, (ii) evaluating the effects of multiple learning experiences upon subsequent higher-order learning, and (iii) investigating whether administration of drugs will improve learning/memory; and (3) apply the techniques and procedures in (1) and (2) above to the experimental animals being investigated by the Anatomy and Immunology research components of this grant. The proposed research will produce an extensive behavioral characterization of animals prone to developing autoimmune disease with and without developmental brain anomalies; will do the same for subjects with induced autoimmunity or experimentally produced minor cortical malformations; and will determine the amount of learning improvement that can be expected in autoimmune and ectopic animals (both spontaneously occurring and experimentally produced) from environmental and pharmacological interventions, singly and jointly. These findings will add to our knowledge of the immune-defective mouse as a useful experimental model for specific developmental learning disabilities such as dyslexia.

两种自身免疫小鼠菌株NZB和BXSB的发生率为40-48％ 皮质性骨质和相关的行为缺陷。 研究 过去五年发现（1）左右爪子异位小鼠不同 关于空间和非空间关联学习任务； （2）与 自身免疫性显着降低了回避学习评分； （3） 早期开发期间暴露于丰富的环境会促进 在非调节和异位小鼠中学习，有一些证据表明非 - 异位从体验中获利更多； （4）子宫的性质 环境（是否自身免疫）显着影响 后代的自身免疫性和随后的回避学习。 这 提案以这些发现为基础，并具有以下目的：（1） 制定一组高阶学习任务，以更彻底地区分 患有生物异常的人（自身免疫性和鼻）； （2） 调查促进学习的程序，包括（i）扩展 早期丰富经验，（ii）评估多重的影响 随后的高阶学习时学习经验，以及（iii） 研究药物的给药是否会改善学习/记忆； （3）将上述（1）和（2）中的技术和程序应用于 解剖学和免疫学研究实验动物 这笔赠款的研究组成部分。 拟议的研究将产生广泛的行为表征 有或没有的动物容易发生自身免疫性疾病 发育性大脑异常；对于有诱导的受试者会做同样的事情 自身免疫性或实验性产生的小皮质畸形；和 将确定可以预期的学习量 自身免疫和异位动物（均自发发生， 通过环境和药理产生的实验生产 干预，单独而共同。 这些发现将增加我们的 了解免疫缺陷小鼠作为有用的实验模型 特定的发展学习障碍，例如阅读障碍。