Complementary Roles of the Hippocampus and the Dorsomedial Striatum during Spatial and Sequence-Based Navigation Behavior

We investigated the neural bases of navigation based on spatial or sequential egocentric representation during the completion of the starmaze, a complex goal-directed navigation task. In this maze, mice had to swim along a path composed of three choice points to find a hidden platform. As reported previously, this task can be solved by using two hippocampal-dependent strategies encoded in parallel i) the allocentric strategy requiring encoding of the contextual information, and ii) the sequential egocentric strategy requiring temporal encoding of a sequence of successive body movements associated to specific choice points. Mice were trained during one day and tested the following day in a single probe trial to reveal which of the two strategies was spontaneously preferred by each animal. Imaging of the activity-dependent gene c-fos revealed that both strategies are supported by an overlapping network involving the dorsal hippocampus, the dorsomedial striatum (DMS) and the medial prefrontal cortex. A significant higher activation of the ventral CA1 subregion was observed when mice used the sequential egocentric strategy. To investigate the potential different roles of the dorsal hippocampus and the DMS in both types of navigation, we performed region-specific excitotoxic lesions of each of these two structures. Dorsal hippocampus lesioned mice were unable to optimally learn the sequence but improved their performances by developing a serial strategy instead. DMS lesioned mice were severely impaired, failing to learn the task. Our data support the view that the hippocampus organizes information into a spatio-temporal representation, which can then be used by the DMS to perform goal-directed navigation.本研究探究了小鼠在完成星型迷宫（Starmaze）这一复杂目标导向导航任务时，基于空间或序列自我中心表征的导航行为的神经基础。该迷宫任务要求小鼠沿包含三个选择节点的路径游泳，以找到隐藏的逃生平台。此前已有研究表明，该任务可通过两种并行编码的海马依赖策略完成：一是需要对情境信息进行编码的异中心策略（allocentric strategy），二是需要对与特定选择节点相关的连续肢体运动序列进行时序编码的序列自我中心策略。研究人员让小鼠接受为期一天的训练，并于次日通过单次探测试验，揭示每只小鼠自发偏好的策略类型。通过对活动依赖基因c-fos的成像分析发现，两种策略均由共享的脑网络所支撑，该网络涉及背侧海马、背内侧纹状体（DMS）以及内侧前额叶皮层。当小鼠使用序列自我中心策略时，其腹侧CA1亚区的激活水平显著升高。为探究背侧海马与DMS在这两类导航任务中可能存在的不同作用，研究人员对这两种脑结构分别进行了区域特异性兴奋性毒素损伤。背侧海马损伤的小鼠无法最优地习得该序列，但通过形成序列策略反而提升了任务表现；而DMS损伤的小鼠则出现严重功能缺损，无法完成该任务的学习。本研究数据支持如下观点：海马可将信息组织为时空表征，随后DMS可利用该表征完成目标导向的导航任务。