The neural circuit basis of infantile amnesia

我的研究项目的总体目标是了解大脑如何存储和处理信息。这个程序由两个不重叠的组件组成。第一部分涉及疾病状态下信息处理的改变，并得到CIHR的支持。第二个部分涉及理解信息处理的基本机制生物学，并得到NSERC的支持。自2005年以来，NSERC一直支持我的实验室在这些基础和基本大脑过程方面的工作。当前的更新——聚焦于记忆的发展方面——与我们由cihr资助的与健康相关的工作在概念上或预算上没有重叠。为什么我们会忘记最早的记忆？这种现象被称为婴儿健忘症，心理学家对其进行了广泛的研究，并形成了一种普遍的模式。作为成年人，我们可以记得童年的许多事件。然而，我们几乎不记得生命最初3-4年发生的任何事情。关于婴儿失忆症的心理学理论强调，语言、自我认同和心智理论等事物与对生活中重要事件形成持久记忆的新兴能力共同出现。然而，非人类哺乳动物在婴儿期也表现出加速遗忘，这表明这种现象不太可能完全用人类特有的概念来解释。相反，其他人认为，大脑发育迟缓可能会干扰对事件进行稳定编码和存储记忆的能力。我的NSERC更新的目标是确定大脑长期发育的特征是导致婴儿健忘症的原因。内侧前额叶皮层（mPFC）在事件记忆的编码和巩固中起着重要作用，并且mPFC的远端连通性在发育过程中不断发展。在这里，我们将测试一个特定的假设，即后期形成的投射（例如，mPFC- >基底外侧杏仁核）的出现与对事件形成持久记忆的能力有因果关系。我们将在整个发育过程中表征mPFC远程连接的结构和功能连接，并询问在老年小鼠中光遗传学上禁用这些连接是否会使它们回归到快速遗忘事件记忆的年轻状态。我们将进一步探究婴儿健忘症的性别和物种差异是否也与这些晚期形成的mPFC远程连接的不同成熟率有因果关系。我的实验室为HQP培训提供了良好的环境。我为每位学员制定了个性化的指导计划，强调技术和沟通技巧以及职业发展。在过去的6年里，学员们已经为63种出版物做出了贡献，并在学术和非学术职位上取得了进展。公平、多样性和包容性是我实验室培训理念的核心，我很自豪我实验室的人口统计数据反映了直接外部世界（即多伦多）的人口统计数据。

The overall goal of my research program is to understand how the brain stores and processes information. This program is composed of two non-overlapping components. The first component is concerned with how information processing is altered in disease states, and is supported by CIHR. The second component is concerned with understanding the basic mechanistic biology of information processing, and is supported by NSERC. NSERC has continuously supported my lab's work on these basic and fundamental brain processes since 2005. The current renewal-focused on developmental aspects of memory-has no conceptual or budgetary overlap with our health-related CIHR-funded work. Why do we forget our earliest memories? This phenomenon-termed infantile amnesia-has been characterized extensively by psychologists, and a universal pattern has emerged. As adults, we can remember many events from our childhood. However, we remember hardly any events from the first 3-4 years of our lives. Psychological theories of infantile amnesia emphasize the co-emergence of things like language, self-identity and theory of mind with the emerging ability to form lasting memories for important events in our lives. However, non-human mammals also exhibit accelerated forgetting in infancy indicating that it is unlikely that this phenomenon can be entirely explained using human-specific concepts. Instead, others have argued that protracted brain development may interfere with the ability to stably encode and store memories for events. The goal of my NSERC renewal is to identify features of protracted brain development are responsible for infantile amnesia. The medial prefrontal cortex (mPFC) plays an important role in the encoding and consolidation of event memories, and the long-range connectivity of mPFC evolves across development. Here, we will test the specific hypothesis that the emergence of late-forming projections (e.g., mPFC--> basolateral amygdala) are causally related to the ability to form enduring memories for events. We will characterize structural and functional connectivity of mPFC long-range connections across development, and ask whether optogenetically disabling these connections in older mice regresses them back to a younger state where event memories are rapidly forgotten. We will further ask whether sex and species differences in infantile amnesia are also causally related to differential maturation rates of these late-forming mPFC long-range connections. My lab provides an excellent environment for training HQP. I develop individualized mentorship plans for each trainee that emphasize technical and communication skills and career development. In the past 6 yeas, trainees have contributed to 63 publications, and have moved on to academic and non-academic positions. Equity, diversity and inclusivity is central to my lab training philosophy, and I am proud that demographics within my lab reflect those in the immediate outside world (i.e., Toronto).