Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology. SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.

Hippocampal function relies on the anterior thalamic nuclei, yet the reasons remain poorly understood. While anterior thalamic lesions disrupt parahippocampal spatial signalling, their impact on the subiculum is unknown, despite the importance of this area for hippocampal networks. We recorded subiculum cells in rats with either permanent (N-methyl-D-aspartic acid) or reversible (muscimol) anterior thalamic lesions. The diverse spatial signals normally found in the subiculum, including place cells, disappeared following permanent thalamic lesions and showed marked disruption during transient lesions. Meanwhile, permanent anterior thalamic lesions had no discernible impact on CA1 place fields. Thalamic lesions reduced spatial alternation performance (permanently or reversibly) to chance levels, while leaving a non-spatial recognition memory task unaffected. These findings, which help to explain why anterior thalamic damage is so deleterious for spatial memory, cast a new spotlight on the importance of subiculum function, and reveal its dependence on anterior thalamic signalling.

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