Impact of Toxoplasma infection on brain networks and host behaviour

弓形虫感染对大脑网络和宿主行为的影响

• 批准号: RGPIN-2015-03923
• 负责人: Frankland, Paul
• 金额: $ 5.46万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=651077
• 关键词: Impact; Toxoplasma; infection; brain; networks

***How can one organism take control of another organism's behavior? While this might seem farfetched, the "behavioural manipulation" hypothesis suggests some parasites specifically manipulate host behaviour to enhance their own transmission. In the case ofToxoplasma gondii, an intracellular parasite that forms tissue cysts in the brains of its animal hosts, studies have shown it to be capable of altering the behaviour of rodents such that they become attracted to, rather than fearful of, their feline predators. The immediate advantage for the parasite is that it increases its likelihood of infecting a feline, the parasites definitive host, i.e. it is only within the feline intestine that the sexual phase of its life cycle occurs. While the Toxoplasma life cycle is relatively well characterized, how Toxoplasma alters the behavior of its host is not. My research program will focus on how this form of `mind control' occurs. ****Our short-term goals, described in this proposal, are as follows: (1) To characterize innate fear behaviour in mice following Toxoplasma infection; (2) To characterize brain networks mediating innate fear in infected and non-infected mice; (3) To mimic the effects of Toxoplasma infection by manipulating this innate fear brain network. We have preliminary data suggesting that each of these goals is feasible. ****The studies outlined here focus on inter-species behavioural manipulation. Our long-term goal is to evaluate whether the same principles apply when organisms of the same species influence one another's behaviour (i.e., intra-species behavioural manipulation). For example, in rodents innate and learned fear may be facilitated by social signals. We will test whether these social signals target the same network nodes within innate fear circuits. ***This research program provides a multidisciplinary training environment, with specified roles for postdoctoral fellows, graduate students and undergraduate students. Trainees in my lab play key roles in all stages of the research: from the conception of the question and hypothesis, design of experiments, to data collection and interpretation, and finally to manuscript preparation. Previous trainees from my lab have taken academic positions (e.g., faculty positions, graduate school) as well as non-academic positions (e.g., industry, professional schools).*** **

一种生物如何控制另一种生物的行为？虽然这似乎有些牵强，但“行为操纵”假说表明，一些寄生虫专门操纵宿主的行为来增强它们自己的传播。刚地弓形虫是一种细胞内寄生虫，能在动物宿主的大脑中形成组织囊肿。研究表明，它能够改变啮齿动物的行为，使它们对猫科捕食者产生吸引力，而不是恐惧。这种寄生虫的直接优势是，它增加了感染猫科动物（寄生虫的最终宿主）的可能性，也就是说，只有在猫科动物的肠道内，其生命周期的性阶段才会发生。虽然弓形虫的生命周期是相对较好的特征，弓形虫如何改变其宿主的行为是不清楚的。我的研究计划将集中在这种形式的“精神控制”是如何发生的。****我们的短期目标，在本提案中描述如下：(1)表征弓形虫感染后小鼠的先天恐惧行为；(2)研究感染小鼠和非感染小鼠介导先天恐惧的脑网络特征；(3)通过操纵这种先天恐惧的大脑网络来模拟弓形虫感染的影响。我们有初步的数据表明，这些目标都是可行的。****这里概述的研究重点是物种间行为操纵。我们的长期目标是评估相同的原则是否适用于同一物种的生物体相互影响的行为（即，物种内行为操纵）。例如，在啮齿类动物中，先天和习得的恐惧可能会受到社会信号的促进。我们将测试这些社交信号是否针对先天恐惧回路中的相同网络节点。***本研究项目为博士后、研究生和本科生提供多学科的培养环境。我实验室的实习生在研究的各个阶段都发挥着关键作用：从问题和假设的概念，实验的设计，到数据的收集和解释，最后到论文的准备。我实验室以前的受训者担任过学术职位（例如，教员职位，研究生院）以及非学术职位（例如，工业，专业学校）。* * * * *