The hippocampus is essential for normal memory but does not act in isolation. The anterior thalamic nuclei may represent one vital partner. Using DREADDs, the behavioral consequences of transiently disrupting anterior thalamic function were examined, followed by inactivation of the dorsal subiculum. Next, the anterograde transport of an adeno-associated virus expressing DREADDs was paired with localized intracerebral infusions of a ligand to target specific input pathways. In this way, the direct projections from the anterior thalamic nuclei to the dorsal hippocampal formation were inhibited, followed by separate inhibition of the dorsal subiculum projections to the anterior thalamic nuclei. To assay spatial working memory, all animals performed a reinforced T-maze alternation task, then a more challenging version that nullifies intramaze cues. Across all four experiments, deficits emerged on the spatial alternation task that precluded the use of intramaze cues. Inhibiting dorsal subiculum projections to the anterior thalamic nuclei produced the severest spatial working memory deficit. This deficit revealed the key contribution of dorsal subiculum projections to the anteromedial and anteroventral thalamic nuclei for the processing of allocentric information, projections not associated with head-direction information. The overall pattern of results provides consistent causal evidence of the two-way functional significance of direct hippocampal-anterior thalamic interactions for spatial processing. At the same time, these findings are consistent with hypotheses that these same, reciprocal interactions underlie the common core symptoms of temporal lobe and diencephalic anterograde amnesia.

SIGNIFICANCE STATEMENT It has long been conjectured that the anterior thalamic nuclei might be key partners with the hippocampal formation and that, respectively, they are principally responsible for diencephalic and temporal lobe amnesia. However, direct causal evidence for this functional relationship is lacking. Here, we examined the behavioral consequences of transiently silencing the direct reciprocal interconnections between these two brain regions on tests of spatial learning. Disrupting information flow from the hippocampal formation to the anterior thalamic nuclei and vice versa impaired performance on tests of spatial learning. By revealing the conjoint importance of hippocampal-anterior thalamic pathways, these findings help explain why pathology in either the medial diencephalon or the medial temporal lobes can result in profound anterograde amnesic syndromes.

海马对于正常的记忆是必不可少的，但并不是孤立地起作用。丘脑前核可能代表一个重要的伴侣。使用DREADD，检查了短暂破坏前丘脑功能的行为后果，然后使背侧下丘脑失活。接下来，表达腺相关病毒的DREADDs的顺行运输与配体的局部脑内输注配对，以靶向特定的输入途径。以这种方式，抑制了从丘脑前核到背侧海马结构的直接投射，然后分别抑制了背侧丘脑背突到丘脑前核的投射。为了分析空间工作记忆，所有动物都执行了增强的T迷宫交替任务，然后执行更具挑战性的版本以使迷宫提示无效。在所有四个实验中，空间交替任务出现了缺陷，这使得无法使用迷宫线索。抑制丘脑前核后背突突产生最严重的空间工作记忆障碍。这种缺陷揭示了背侧下丘脑投射对前外侧丘脑核和前丘脑丘脑核的重要贡献，以处理同心异体信息，这些投射与头部信息无关。结果的整体模式提供了直接的海马-前丘脑相互作用对空间处理的双向功能意义的一致因果证据。同时，这些发现与以下假设相符：这些相同的相互影响是颞叶和双脑顺行性健忘症的共同核心症状。

重要性声明长期以来人们一直猜测，丘脑前核可能是海马结构的关键伙伴，并且它们分别负责双脑和颞叶健忘症。但是，缺乏这种功能关系的直接因果证据。在这里，我们研究了在空间学习测试中暂时沉默这两个大脑区域之间的直接相互联系的行为后果。从海马形成到丘脑前核的信息流中断，反之亦然，这削弱了空间学习测试的性能。通过揭示海马-前丘脑通路的共同重要性，