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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717981
• 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，为导航和情景记忆生成空间上下文地图。侧隔（LS）是海马形成的主要皮层下靶点，接受来自锥体神经元CA3、CA2、CA1和耻骨下神经元的大量投射。尽管从海马体接收了大量的投射，但左脑区接收的信息的性质以及海马体-左脑回路的组织在很大程度上仍然是未知的。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，然后将其传递给ms。我们的目标是根据其解剖连接和与海马形成的假设功能关系以及它们对ms的输出来表征LS细胞的空间放电特性。所有实验均在开放场，目标导向导航任务以及自由行为小鼠的记忆依赖任务中进行。