Genetic and environmental determinants of sensory, motor, social and cognitive functions in mice

我的研究包括五个主要项目，都涉及到小鼠的行为表型。每个项目的目标如下：(1)神经退行性疾病和其他疾病的小鼠模型的可靠性和有效性如何？当一只转基因老鼠被开发成脆性X染色体障碍、阿尔茨海默病、多动症或其他人类疾病的模型时，我们如何确定它们的神经行为异常？我们将使用我们的行为测试电池来测试提出的小鼠模型，以确定它们的哪些行为是正常的，哪些是异常的，以及它们的行为如何随着年龄的增长而变化。(2)小鼠的感觉能力如何影响其认知表现？许多常用的近交系小鼠都有与年龄相关的视觉和/或听觉障碍。我们将使用我们的行为分析将感觉功能障碍与认知缺陷分离开来，这样我们就可以确定小鼠是认知受损（阿尔茨海默氏症模型小鼠）还是有感觉功能障碍（失明小鼠）。(3)设备设计和测试程序对小鼠行为的影响是什么？本研究将研究巴恩斯圆形迷宫、集合转移范式、五选择系列反应时间任务、赫布-威廉姆斯迷宫和八臂径向迷宫中小鼠行为的实验装置和程序设计如何影响小鼠的学习记忆策略和焦虑样行为。(4)转基因小鼠的神经变化如何与行为变化相关？当我们发现有行为异常的转基因小鼠时，我们将通过免疫特异性染色检查大脑组织学，观察细胞存活、细胞死亡（凋亡）、轴突和树突大小、突触数量和神经化学活性（ACh、AChE、DA、NE、5-HT）的变化，来研究这些异常的神经基础。(5)小鼠行为实验的错误率是多少？如何检测、测量和减少错误？“实验室效应”在小鼠行为研究的差异中占很大比例。我们将检查实验者，老鼠，程序和设备变量导致不同的结果，当同一实验在不同时间在同一实验室进行。

My research consists of five major projects, all of which involve the behavioural phenotyping of mice. The objectives of each project are as follows: (1) How reliable and valid are mouse models of neurodegenerative and other diseases? When a genetically modified mouse is developed as a model for Fragile X disorder, Alzheimer's Disease, ADHD or other human disorders, how can we determine their neuro-behavioural abnormalities? We will use our behavioural test battery to test proposed mouse models to determine which of their behaviours are normal, which are abnormal and how their behaviours change with age. (2) How do the sensory abilities of mice affect their cognitive performance? Many commonly used inbred strains of mice have age-related visual and/or auditory impairments. We will use our behavioural assays to dissociate sensory malfunction from cognitive deficits so that we can determine whether a mouse is cognitively impaired (an Alzheimer's model mouse) or has a sensory malfunction (a blind mouse). (3) What are the effects of apparatus design and test procedure on mouse behaviour? We will study how the design of test apparatus and procedures for studying mouse behaviour in the Barnes circular maze, the set-shifting paradigm, the 5-choice serial reaction time task, Hebb-Williams maze and 8-arm radial maze effects learning and memory strategies and anxiety-like behaviour in mice. (4) How do neural changes in transgenic mice correlate with behavioural changes? When we find a transgenic mouse with behavioural abnormalities, we will investigate the neural basis of these abnormalities by examining the brains histologically with immunospecific stains for changes in cell survival, cell death (apoptosis), axon and dendrite size, number of synapses and for neurochemical activity (ACh, AChE, DA, NE, 5-HT). (5) What is the error rate in mouse behavioural experiments and how can errors be detected, measured and reduced? "Laboratory effects" account for a high proportion of the variance in mouse behavioural studies. We will examine experimenter, mouse, procedural and apparatus variables which lead to different results when the same experiment is performed at different times in the same laboratory.