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

海马体处理空间信息，以生成导航和情景记忆的空间背景地图。外侧隔(LS)是海马结构的主要皮质下靶点，接受CA3、CA2、CA1锥体神经元和下丘脑神经元的大量投射。尽管从海马区收到了大量的投射，但LS所接收的信息的性质以及海马区LS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LS的解剖位置，它可能参与空间和奖励信号的整合，然后传递给MS。使用尖端病毒跟踪技术、光遗传学、带有微型荧光显微镜的新钙成像技术和电生理学，我们的目标是基于LS细胞的解剖联系和假想的与海马结构的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。 总体目标：该研究计划将参照外侧隔区不同亚核的解剖联系和假想的与海马体的功能关系来确定它们的空间编码特性，并确定这些投射在空间导航和奖赏寻求中的行为相关性。我们将利用光遗传学来确定LS是如何因果作用于这些功能的。 具体目标：我们将确定这个微回路在建立、维持和更新语境和奖赏之间的必要联系方面的具体作用，重点是外侧隔的整合作用。 1.研究LS相对于其传入投射的解剖细分，重点关注海马结构的不同区域，以及它们向内侧隔区特定神经元类型的输出。 2.根据这些外侧隔细胞与海马体的功能关系，建立它们的空间放电特征。我们将使用最先进的钙成像技术和微型显微镜，并结合最近开发的病毒跟踪策略。 3.利用光遗传学，我们将操纵LS回路，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赏方面具有重要作用。 这一研究计划的结果将首次揭示LS神经元的功能特征，这些神经元与来自海马区的传入输入直接相关，并独立于海马区的不同亚区。这些强大的技术的结合将提供对LS神经元在记忆中的作用的清楚了解。

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.