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？虽然这看起来可能有些牵强，但“行为操纵”假说表明，某些寄生虫专门操纵宿主的行为来增强自身的传播能力。在弓形虫的案例中，研究表明，它能够改变啮齿动物的行为，使它们被猫科动物的捕食者吸引，而不是害怕。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包囊。寄生虫的直接优势是它增加了感染猫的可能性，猫是寄生虫的最终宿主，即只在猫的肠道内发生其生命周期的有性阶段。虽然弓形虫的生命周期具有相对较好的特征，但弓形虫如何改变其宿主的行为却没有。我的研究计划将重点放在这种“精神控制”是如何发生的。 在这项建议中，我们的短期目标如下：(1)表征弓形虫感染后小鼠的先天恐惧行为；(2)表征在感染和未感染的小鼠中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。我们有初步数据表明，这些目标中的每一个都是可行的。 这里概述的研究重点是物种间的行为操纵。我们的长期目标是评估当同一物种的生物体相互影响彼此的行为(即物种内的行为操纵)时，同样的原则是否适用。例如，啮齿动物与生俱来的恐惧和后天的恐惧可能是由社会信号促成的。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。 该研究计划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特定的角色。我实验室的学员在研究的所有阶段都发挥了关键作用：从问题和假设的构思，实验设计，到数据收集和解释，最后到手稿准备。我实验室以前的实习生都曾担任过学术职位(例如，教员职位、研究生院)和非学术职位(例如，行业、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).