To improve the translational predictability of treatment strategies for Huntington’s disease (HD), sensitive and analogous cognitive outcomes are needed across HD animal models and humans. Spatial memory measures are promising candidates because they are based on ‘visual’ or ‘non-verbal’ cognition, and are commonly tested in both animals and humans. Here, we consider the suitability of spatial memory for strengthening translational links between animals and humans in HD research and clinical trials. We describe findings of spatial memory impairments in human HD and mouse models, including which aspects of spatial memory are most affected and at which time points in disease progression. We also describe the neural systems that underlie spatial memory and link spatial memory impairments to HD neuropathology, focussing on striatal and hippocampal systems. We provide a critical analysis of the literature in terms of the suitability of spatial memory for bridging the translational gap between species. Finally, we discuss possible neural mechanisms that might explain the spatial memory impairments seen in HD, and their relevance to potential treatments.

为了提高亨廷顿病 (HD) 治疗策略的转化可预测性，需要在 HD 动物模型和人类中获得敏感和类似的认知结果。空间记忆测量是有希望的候选者，因为它们基于“视觉”或“非语言”认知，并且通常在动物和人类中进行测试。在这里，我们考虑空间记忆在 HD 研究和临床试验中加强动物和人类之间的转化联系的适用性。我们描述了人类 HD 和小鼠模型中空间记忆障碍的发现，包括空间记忆的哪些方面受影响最大以及疾病进展的哪些时间点。我们还描述了构成空间记忆的神经系统，并将空间记忆障碍与 HD 神经病理学联系起来，专注于纹状体和海马系统。我们就空间记忆是否适合弥合物种之间的翻译鸿沟对文献进行了批判性分析。最后，我们讨论了可能解释 HD 中出现的空间记忆障碍的可能神经机制，以及它们与潜在治疗的相关性。