The neural circuit basis of infantile amnesia

我的研究计划的总体目标是了解大脑如何存储和处理信息。该方案由两个不重叠的部分组成。第一个组成部分是关于信息处理是如何改变疾病状态，并支持CIHR。第二部分是关于理解信息处理的基本机制生物学，并由NSERC支持。自2005年以来，NSERC一直支持我的实验室在这些基本和基础大脑过程方面的工作。目前的更新，集中在发展方面的记忆，没有概念或预算重叠与我们的健康相关的CIHR资助的工作。 为什么我们会忘记最早的记忆？这种现象被称为婴儿期健忘症，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，我们可以记住我们童年的许多事件。然而，我们几乎不记得我们生命中最初3 - 4年的任何事件。婴儿健忘症的心理学理论强调语言、自我认同和心理理论等事物的共同出现，以及对我们生活中重要事件形成持久记忆的能力的出现。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，大脑发育的延长可能会干扰稳定编码和存储事件记忆的能力。我的NSERC更新的目标是确定延长大脑发育的特征是婴儿健忘症的原因。内侧前额叶皮层（mPFC）在事件记忆的编码和巩固中起着重要的作用，其长距离连接在整个发育过程中不断演变。在这里，我们将测试特定的假设，即后期形成的投影的出现（例如，mPFC-->基底外侧杏仁核）与形成对事件的持久记忆的能力有因果关系。我们将描述整个发育过程中mPFC长距离连接的结构和功能连接，并询问光遗传学禁用老年小鼠中的这些连接是否会使它们回归到事件记忆迅速遗忘的年轻状态。我们将进一步询问婴儿健忘症的性别和物种差异是否也与这些晚形成的mPFC长距离连接的不同成熟率有因果关系。 我的实验室为培养HQP提供了极好的环境。我为每个学员制定个性化的指导计划，强调技术和沟通技能以及职业发展。在过去的6年中，受训人员为63份出版物撰稿，并担任学术和非学术职务。公平、多样性和包容性是我实验室培训理念的核心，我很自豪我实验室内的人口统计反映了外部世界的人口统计（即，多伦多）。

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).