Brain lactate formation, intercellular exchange and utilization has been implicated in memory formation. However, the individual role of either neuronal or astroglial monocarboxylate transporters for the acquisition and consolidation of information remains incomplete. Using novel transgenic mice and a viral vector approach to decrease the expression of each transporter in a cell-specific manner within the dorsal hippocampus, we show that both neuronal MCT2 and astroglial MCT4 are required for spatial information acquisition and retention (at 24 h post-training) in distinct hippocampus-dependent tasks. Intracerebral infusion of lactate rescued spatial learning in mice with reduced levels of astroglial MCT4 but not of neuronal MCT2, suggesting that lactate transfer from astrocytes and utilization in neurons contribute to hippocampal-dependent learning. In contrast, only neuronal MCT2 was shown to be required for long-term (7 days post training) memory formation. Interestingly, reduced MCT2 expression levels in mature neurons result in a heterologous effect as it blunts hippocampal neurogenesis associated with memory consolidation. These results suggest important but distinct contributions of both neuronal MCT2 and astroglial MCT4 in learning and memory processes, going beyond a simple passive role as alternative energy substrate suppliers or in waste product disposal.

脑乳酸形成、细胞间交换和利用与记忆形成有关。然而，神经元或星形胶质单羧酸转运蛋白在信息获取和整合方面的个人作用仍然不完整。使用新型转基因小鼠和病毒载体方法以细胞特异性方式降低背海马内每个转运蛋白的表达，我们表明神经元 MCT2 和星形胶质细胞 MCT4 都是空间信息获取和保留所必需的（在 24 小时后训练）在不同的海马体依赖任务中。脑内注射乳酸挽救了星形胶质细胞 MCT4 水平降低但神经元 MCT2 水平降低的小鼠的空间学习，表明来自星形胶质细胞的乳酸转移和神经元的利用有助于海马依赖性学习。相比之下，只有神经元 MCT2 被证明是长期（训练后 7 天）记忆形成所必需的。有趣的是，成熟神经元中 MCT2 表达水平的降低会导致异源效应，因为它会减弱与记忆巩固相关的海马神经发生。这些结果表明神经元 MCT2 和星形胶质细胞 MCT4 在学习和记忆过程中的重要但不同的贡献，超越了作为替代能源底物供应商或废物处理的简单被动角色。成熟神经元中 MCT2 表达水平的降低会导致异源效应，因为它会减弱与记忆巩固相关的海马神经发生。这些结果表明神经元 MCT2 和星形胶质细胞 MCT4 在学习和记忆过程中的重要但不同的贡献，超越了作为替代能源底物供应商或废物处理的简单被动角色。成熟神经元中 MCT2 表达水平的降低会导致异源效应，因为它会减弱与记忆巩固相关的海马神经发生。这些结果表明神经元 MCT2 和星形胶质细胞 MCT4 在学习和记忆过程中的重要但不同的贡献，超越了作为替代能源底物供应商或废物处理的简单被动角色。