Comyn Typhaine, Preat Thomas, Pavlowsky Alice, Plaçais Pierre-Yves
Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, 10 rue Vauquelin, 75005 Paris, France.
Co-corresponding authors.
bioRxiv. 2024 Jun 18:2023.10.06.561186. doi: 10.1101/2023.10.06.561186.
Relevance-based selectivity and high energy cost are two distinct features of long-term memory (LTM) formation that warrant its default inhibition. Spaced repetition of learning is a highly conserved cognitive mechanism that can lift this inhibition. Here, we questioned how the spacing effect integrates experience selection and energy efficiency at the cellular and molecular levels. We showed in that spaced training triggers LTM formation by extending over several hours an increased mitochondrial metabolic activity in neurons of the associative memory center, the mushroom bodies (MBs). We found that this effect is mediated by PKCδ, a member of the so-called 'novel PKC' family of enzymes, which uncovers the critical function of PKCδ in neurons as a regulator of mitochondrial metabolism for LTM. Additionally, PKCδ activation and translocation to mitochondria result from LTM-specific dopamine signaling on MB neurons. By bridging experience-dependent neuronal circuit activity with metabolic modulation of memory-encoding neurons, PKCδ signaling binds the cognitive and metabolic constraints underlying LTM formation into a unified gating mechanism.
基于相关性的选择性和高能量消耗是长期记忆（LTM）形成的两个不同特征，这使得其默认受到抑制。间隔重复学习是一种高度保守的认知机制，可以解除这种抑制。在这里，我们探讨了间隔效应如何在细胞和分子水平上整合经验选择和能量效率。我们在研究中表明，间隔训练通过在数小时内延长联想记忆中心蘑菇体（MBs）神经元中线粒体代谢活性的增加来触发LTM形成。我们发现这种效应是由PKCδ介导的，PKCδ是所谓“新型PKC”酶家族的成员，它揭示了PKCδ在神经元中作为LTM线粒体代谢调节因子的关键功能。此外，PKCδ的激活和向线粒体的转位源于MB神经元上LTM特异性多巴胺信号。通过将经验依赖性神经回路活动与记忆编码神经元的代谢调节联系起来，PKCδ信号将LTM形成背后的认知和代谢限制结合成一个统一的门控机制。
