Mechanisms and circuits underlying the role of the lateral septum brain region in learning and memory

外侧隔脑区在学习和记忆中作用的机制和回路

• 批准号: RGPIN-2020-06717
• 负责人: Williams, Sylvain
• 金额: $ 4.01万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763681
• 关键词: Mechanisms; circuits; underlying; role; lateral

The hippocampus processes spatial information for generating spatial contextual maps for navigation and episodic memory. The lateral septum (LS) is the main subcortical target of the hippocampal formation, receiving massive projections from the pyramidal neurons of CA3, CA2, CA1 and subiculum neurons. Despite receiving massive projections from the hippocampus, the nature of the information the LS is receiving, and the organization of hippocampal-LS circuits remains largely unknown. The LS is part of an extensive outer layer covering the medial septum (MS) which contains neurons that use GABA as their neurotransmitter. Because of its anatomical position, the LS may be involved in the integration of spatial and rewarding signals which is then passed on to the MS. Using cutting edge viral tracing techniques, optogenetics, new calcium imaging techniques with miniaturized fluorescence microscopy, and electrophysiology, we aim to characterize the spatial firing properties of cells in the LS based upon their anatomical connections and hypothesized functional relationship with the hippocampal formation and their output to the MS. All experiments in open field, goal directed navigation tasks, as well as memory-dependent tasks in freely behaving mice. General objective: The research program will determine the spatial coding properties of the different sub nuclei of the lateral septum, in reference to their anatomical connections and hypothesized functional relationship with the hippocampus and define the behavioral correlates of these projections in spatial navigation and reward seeking. We will determine using optogenetics how the LS causally contributes to these functions. Specific objectives: We will determine the specific role of this microcircuit in building, maintaining and updating the necessary associations between context and reward, focusing on the integrative role of the lateral septum. 1. Investigate the anatomical subdivisions of the LS with respect to its incoming projections, focusing on the different areas of the hippocampal formation, as well as their output to specific neuronal types in the medial septum. 2. Establish the spatial firing characteristics of these lateral septal cells in reference to their functional relationship with the hippocampus. We will use state-of-the-art calcium imaging techniques with miniature microscope combined with recently developed viral tracing strategies. 3. Using optogenetics, we will manipulate the LS circuits to provide causal evidence that LS neurons have an essential role in spatial navigation and memory as well as integrating space and reward. The results of this research program will reveal for the first time the functional features of LS neurons in direct relation to the incoming input from the hippocampus and independently from the different hippocampal subregions. The combination of these powerful techniques will provide a clear understanding of the role of LS neurons in memory.

海马体处理空间信息以生成用于导航和情景记忆的空间上下文图。外侧隔（LS）是海马结构的主要皮质下靶区，接受来自CA 3、CA 2、CA 1锥体神经元和下托神经元的大量投射。尽管从海马体接收到大量的投射，但LS接收的信息的性质以及海马体-LS电路的组织仍然在很大程度上未知。LS是覆盖内侧隔（MS）的广泛外层的一部分，其中包含使用GABA作为其神经递质的神经元。由于其解剖位置，LS可能参与空间和奖励信号的整合，然后将其传递到MS。使用尖端病毒追踪技术，光遗传学，新型钙成像技术与小型荧光显微镜和电生理学，我们的目的是根据LS中细胞的解剖学连接和与细胞的假设功能关系来表征LS中细胞的空间放电特性。海马结构及其向MS的输出。所有实验均在自由行为小鼠中进行开放视野、目标导向导航任务以及记忆依赖性任务。总体目标：该研究计划将确定侧隔不同亚核的空间编码特性，参考它们与海马的解剖学连接和假设的功能关系，并定义这些投射在空间导航和奖励寻求中的行为相关性。我们将使用光遗传学来确定LS如何因果地促进这些功能。 具体目标：我们将确定这个微回路在建立，维持和更新上下文和奖励之间的必要关联方面的具体作用，重点是侧隔的整合作用。1.研究LS的解剖学细分与其传入的预测，重点是海马结构的不同区域，以及它们的输出到特定的神经元类型在内侧隔。2.建立这些侧隔细胞的空间放电特征，参考它们与海马的功能关系。我们将使用最先进的钙成像技术与微型显微镜结合最近开发的病毒追踪策略。3.利用光遗传学，我们将操纵LS电路，以提供因果证据，证明LS神经元在空间导航和记忆以及整合空间和奖励中起着至关重要的作用。这项研究计划的结果将首次揭示LS神经元的功能特征，这些功能特征与来自海马的传入输入直接相关，并且独立于不同的海马子区域。结合这些强大的技术将提供一个清晰的理解LS神经元在记忆中的作用。