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，所有这些项目都涉及小鼠的行为表型。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？当转基因小鼠被开发为脆性X染色体疾病、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拟议的小鼠模型，以确定它们的行为中哪些是正常的，哪些是异常的，以及它们的行为如何随年龄变化。(2)老鼠的感觉能力如何影响它们的认知能力？许多常用的近交系小鼠具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测定将感觉功能障碍与认知缺陷分离，以便我们可以确定小鼠是否认知受损（阿尔茨海默病模型小鼠）或具有感觉功能障碍（盲小鼠）。(3)仪器设计和测试程序对小鼠行为有什么影响？我们将研究在巴恩斯环形迷宫、集合转移范式、5选择系列反应时间任务、Hebb-Williams迷宫和8臂径向迷宫中研究小鼠行为的测试装置和程序的设计如何影响小鼠的学习和记忆策略以及焦虑样行为。(4)转基因小鼠的神经变化如何与行为变化相关？当我们发现一个转基因小鼠的行为异常，我们将研究这些异常的神经基础，通过检查脑组织学与免疫特异性染色的变化，细胞存活，细胞死亡（凋亡），轴突和树突的大小，突触的数量和神经化学活性（乙酰胆碱酯酶，乙酰胆碱酯酶，DA，NE，5-羟色胺）。(5)小鼠行为实验中的错误率是多少？如何检测、测量和减少错误？“实验室效应”在小鼠行为研究中占很大比例。我们将研究实验者，小鼠，程序和仪器变量，导致不同的结果时，在同一实验室在不同的时间进行相同的实验。

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.