Investigating the role of the claustrum in social memory

社会互动是人类和动物生存的一个重要方面。然而，我们目前对大脑中支持社会信息处理的细胞机制知之甚少。我实验室的总体目标是了解社会记忆背后的神经回路。由于小鼠是社会性动物，它们提供了用于破译大脑如何编码、存储和回忆社会信息的理想系统。小鼠模型提供了在社会行为期间以优异的时间分辨率记录神经活动和行为的能力，以及使用现有技术分子工具以细胞类型或途径特异性方式精确操纵神经活动的能力。** 一般认为，社会认知依赖于一系列大脑网络，包括前额叶皮层、杏仁核和颞叶区域，如海马体。最近的研究使用了一种无偏见的全脑屏幕，表明大脑腹侧部分的其他区域被社会刺激激活。这项工作，加上我们自己的发现，已经集中在一个对社会刺激有强烈反应的小结构上，重要的是，与已知也被相同的社会线索激活的其他大脑区域有异常密集的连接。这种结构被称为屏状核（CLA）。CLA本身就很有趣，因为研究人员几十年来一直在猜测它的功能。弗朗西斯克里克认为，CLA可能是大脑中意识的中心，因为它具有广泛的连接性。然而，CLA由于其体积小而难以研究。我们已经开发出一种方法来专门记录和操纵CLA活动，并使用这些工具，目前的建议旨在了解CLA如何在社会记忆的背景下发挥作用。***首先，我们将确定连接CLA和社交脑区域的解剖学通路，并确定这些区域如何相互作用，以及哪些通路在社交信息处理过程中特别活跃。第二，我们将在自由活动的小鼠中使用最先进的体内钙成像，以测量社交记忆任务期间的CLA活性。最后，使用细胞类型和通路特异性光遗传学实验，我们将确定CLA如何与其他大脑区域（如前额叶皮层）通信的生理机制，并确定该结构在社会行为中的任何因果作用。社会信息处理障碍出现在阿尔茨海默病和自闭症谱系障碍等疾病状态中，这两种疾病在加拿大和其他发达国家都在上升。因此，了解社会大脑如何运作的基本知识，对于理解和治疗这些疾病的能力至关重要。*****

Social interaction is an important facet of human and animal existence. However, we currently know very little about the cellular mechanisms in the brain that support social information processing. The overall goal of my lab is to understand the neural circuitry underlying social memory. As mice are social animals they provide the ideal system for deciphering how the brain encodes, stores, and recalls social information Mice models provide the ability to record neural activity and behavior with exceptional temporal resolution during social behaviors, and the ability to precisely manipulate neural activity in a cell type, or pathway specific manner using state of the art molecular tools. ******There is a general understanding that social cognition relies on a set of brain networks which include the prefrontal cortex, the amygdala, and areas of the temporal lobe such as the hippocampus. More recent work using an unbiased, brain-wide screen, suggests that other regions within the ventral-lateral portion of the brain are activated by social stimuli. This work, together with our own findings, have converged upon a small structure with strong responses to social stimuli, and importantly, with exceptional dense connectivity with other brain regions known to also be activated by the same social cues. This structure is referred to as the claustrum (CLA). The CLA is interesting in its own right, as researchers have speculated about its function for decades. Francis Crick suggested that the CLA may be the center of consciousness in the brain, due to its extensive wide ranging connectivity. However, the CLA is incredibly hard to study due to its small size. We have developed a method to specifically record and manipulate CLA activity, and using these tools, the current proposal seeks to understand how the CLA functions in the context of social memory. ******The following proposal consists of three main goals. First, we will determine the anatomical pathways connecting the CLA to areas of the the social brain' and determine how these regions interact, and which pathways are especially active during social information processing. Second, we will use state of the art in vivo calcium imaging in freely moving mice, in order to measure CLA activity during social memory tasks. Finally using cell type and pathway specific optogenetic experiments we will determine the physiological mechanisms underlying how the CLA communicates with other brain regions such as the prefrontal cortex and determine any causal role of this structure in social behavior. Impairments in social information processing arise in disease states such as Alzheimer's disease and Autism spectrum disorder both of which are on the rise in Canada and other developed countries. Therefore, basic knowledge of how the social brain' operates, is central to the ability to understand and treat these disorders. *****