The process of memory consolidation is energy-demanding and brain energy deficits result in memory impairments. Indeed, L-lactate, a preferred neuronal energy substrate, enhances the formation of memory, while blockade of the neuronal uptake of L-lactate by either pharmacological means or using its enantiomer D-lactate, impairs memory. Beyond metabolism, both enantiomers of lactate also have signaling properties through the hydroxycarboxylic acid receptor 1 (HCAR1). Thus far, paradigms testing for an effect of lactate on memory modulation have ignored HCAR1 signaling while also mainly performing manipulations before learning and using intracranial administration techniques. Using an inhibitory avoidance (IA) memory protocol, the present study examined the effects of systemic administration of both L- and D-lactate as well as the specific HCAR1 agonist 3,5-dihydroxybenzoic acid (3,5-DHBA) across pre- and post-training periods. We found that post-training subcutaneous injections of either 3,5-DHBA or D-lactate significantly enhanced memory compared to saline controls, whereas L-lactate had no effect, suggesting that HCAR1 signaling in the absence of lactate metabolism supports memory consolidation processes. When administered 15 minutes prior to training, D-lactate and 3,5-DHBA impaired memory compared to saline controls. In contrast, L-lactate treated rats showed memory enhancements as compared to D-lactate-treated rats. Taken together, these results suggest different roles for lactate at different memory stages. It is likely that a metabolic role is at play during learning while HCAR1 signaling may play a greater role during consolidation.

中文翻译：

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L-和D-乳酸对记忆编码和整合的不同作用：HCAR1信号的潜在作用。

记忆整合的过程需要能量，而脑能量不足会导致记忆障碍。实际上，优选的神经元能量底物L-乳酸盐增强了记忆的形成，而通过药理学手段或其对映异构体D-乳酸盐来阻断L-乳酸盐的神经元摄取会损害记忆。除代谢外，乳酸的两种对映异构体还具有通过羟基羧酸受体1（HCAR1）发出信号的特性。迄今为止，关于乳酸对记忆调节的作用的范例测试已经忽略了HCAR1信号传导，同时还主要在学习和使用颅内给药技术之前进行了操作。使用禁止回避（IA）记忆协议，本研究检查了L-和D-乳酸盐以及特定HCAR1激动剂3,5-二羟基苯甲酸（3,5-DHBA）在训练前后的全身给药效果。我们发现，与盐水对照组相比，皮下注射3,5-DHBA或D-乳酸盐的皮下注射显着增强了记忆，而L-乳酸盐则没有作用，这表明在缺乏乳酸代谢的情况下HCAR1信号传导支持记忆巩固过程。与训练前相比，在训练前15分钟服用D-乳酸和3,5-DHBA会损害记忆。相反，与D-乳酸盐处理的大鼠相比，L-乳酸盐处理的大鼠显示出记忆增强。综上所述，这些结果表明乳酸在不同记忆阶段的作用不同。