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。我的实验室的总体目标是了解社会记忆背后的神经回路。由于小鼠是群居动物，它们为破译大脑如何编码、存储和回忆社会信息提供了理想的系统。小鼠模型提供了以特殊的时间分辨率记录社交行为期间的神经活动和行为的能力，以及使用最先进的分子工具以细胞类型或特定路径的方式精确操纵神经活动的能力。人们普遍认为，社会认知依赖于一系列大脑网络，包括前额叶皮质、杏仁核和海马体等颞叶区域。最近的一项使用无偏见的全脑屏幕的研究表明，社会刺激会激活大脑腹侧侧部的其他区域。这项工作与我们自己的发现结合在一起，形成了一个对社会刺激有强烈反应的小结构，重要的是，它与已知也被相同的社会线索激活的其他大脑区域有着异常密集的连接。这种结构被称为屏蔽层(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可能是大脑的意识中心，因为它具有广泛的连通性。然而，由于CLA的规模很小，研究起来非常困难。我们已经开发了一种专门记录和操纵CLA活动的方法，并使用这些工具，当前的提案试图了解CLA在社会记忆背景下是如何发挥作用的。*以下提议包括三个主要目标。首先，我们将确定连接CLA和社交大脑区域的解剖路径，并确定这些区域如何相互作用，以及哪些路径在社交信息处理过程中特别活跃。其次，我们将在自由活动的小鼠身上使用最先进的活体钙成像，以测量社会记忆任务中的CLA活动。最后，利用细胞类型和特定路径的光遗传学实验，我们将确定CLA如何与其他大脑区域(如前额叶皮质)通信的生理机制，并确定这种结构在社会行为中的任何因果作用。社会信息处理的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是至关重要的。*****

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. *****