SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan.
SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan
Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16080-16085. doi: 10.1073/pnas.1901292116. Epub 2019 Jul 23.
Memory consolidation is augmented by repeated learning following rest intervals, which is known as the spacing effect. Although the spacing effect has been associated with cumulative cellular responses in the neurons engaged in memory, here, we report the neural circuit-based mechanism for generating the spacing effect in the memory-related mushroom body (MB) parallel circuits in To investigate the neurons activated during the training, we monitored expression of phosphorylation of mitogen-activated protein kinase (MAPK), ERK [phosphorylation of extracellular signal-related kinase (pERK)]. In an olfactory spaced training paradigm, pERK expression in one of the parallel circuits, consisting of γm neurons, was progressively inhibited via dopamine. This inhibition resulted in reduced pERK expression in a postsynaptic GABAergic neuron that, in turn, led to an increase in pERK expression in a dopaminergic neuron specifically in the later session during spaced training, suggesting that disinhibition of the dopaminergic neuron occurs during spaced training. The dopaminergic neuron was significant for gene expression in the different MB parallel circuits consisting of α/βs neurons for memory consolidation. Our results suggest that the spacing effect-generating neurons and the neurons engaged in memory reside in the distinct MB parallel circuits and that the spacing effect can be a consequence of evolved neural circuit architecture.
记忆巩固通过在休息间隔后重复学习来增强,这被称为间隔效应。尽管间隔效应与参与记忆的神经元中的累积细胞反应有关,但在这里,我们报告了基于神经回路的机制,用于在与记忆相关的蘑菇体(MB)平行回路中产生间隔效应。为了研究训练期间激活的神经元,我们监测了有丝分裂原激活蛋白激酶(MAPK)磷酸化,ERK[细胞外信号相关激酶(pERK)磷酸化]的表达。在嗅觉间隔训练范式中,多巴胺逐渐抑制由γm 神经元组成的一个平行回路中的 pERK 表达。这种抑制导致 GABA 能神经元中 pERK 表达减少,进而导致多巴胺能神经元中 pERK 表达增加,特别是在间隔训练的后期,这表明在间隔训练期间发生了多巴胺能神经元的去抑制。多巴胺能神经元对于由α/βs 神经元组成的不同 MB 平行回路中的基因表达是重要的,这对于记忆巩固。我们的结果表明,产生间隔效应的神经元和参与记忆的神经元位于不同的 MB 平行回路中,并且间隔效应可能是进化神经回路结构的结果。