Impact of Toxoplasma infection on brain networks and host behaviour

一个有机体如何控制另一个有机体的行为？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行为，以增强自身的传播。弓形虫是一种细胞内寄生虫，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，使它们对猫科掠食者产生吸引力，而不是恐惧。对寄生虫的直接好处是，它增加了感染猫的可能性，寄生虫的最终宿主，也就是说，它的生命周期的有性阶段只发生在猫的肠道内。虽然弓形虫的生命周期是比较好的特点，弓形虫如何改变其宿主的行为是没有。我的研究项目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，在这个建议中描述，如下：（1）在弓形虫感染后的小鼠中表征先天恐惧行为;（2）在感染和未感染的小鼠中表征介导先天恐惧的大脑网络;（3）通过操纵这种先天恐惧大脑网络来模拟弓形虫感染的影响。我们的初步数据表明这些目标中的每一个都是可行的。 这里概述的研究集中在物种间的行为操纵。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，种内行为操纵）。例如，在啮齿类动物中，天生的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。 该研究项目提供了一个多学科的培训环境，为博士后研究员、研究生和本科生提供了指定的角色。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，实验设计，到数据收集和解释，最后到手稿准备。我实验室以前的学员都担任过学术职务（例如，教师职位，研究生院）以及非学术职位（例如，工业、专业学校）。

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).