Astrocytic Contributions to Long Term Memory & Synaptic Plasticity

描述（由申请人提供）：记忆巩固是一个过程，通过这个过程，新学到的信息，它存在于一个不稳定的状态，成为一个持久的记忆，是抗中断。长期记忆巩固需要从头蛋白质合成，树突状蛋白质合成很可能也参与了这一过程。长时程增强（LTP）是突触强度的持续增加，被认为是长期记忆的细胞相关性。像记忆巩固一样，LTP的晚期形式（L-LTP）也需要蛋白质合成，并且已经显示出特别需要树突蛋白质合成以及体细胞蛋白质合成。情绪经验的记忆，如那些产生的恐惧条件反射为基础的抑制性回避（IA）范式，受到调制的各种激素。去甲肾上腺素在觉醒时从蓝斑释放，并通过β-肾上腺素能受体增强记忆。LTP也是如此，它同样受到去甲肾上腺素的调节。我们实验室和其他实验室的最新证据表明，星形胶质细胞在学习和记忆以及LTP中发挥的作用比以前认为的要大。星形胶质细胞通过糖原分解和单羧酸转运蛋白转移乳酸到神经元，对记忆巩固和LTP维持至关重要（见初步数据）。有趣的是，β-肾上腺素能受体存在于星形胶质细胞上，并且当受到刺激时也在星形胶质细胞中具有代谢作用。该项目将测试星形胶质细胞对长期记忆和LTP的贡献。具体来说，它将测试的假设，星形胶质细胞通过提供星形胶质细胞-神经元耦合，通过乳酸支持与树突状蛋白合成的激活相关的高能量需求，关键有助于记忆的形成。此外，它将测试的假设，去甲肾上腺素依赖性调节记忆是由星形胶质细胞神经元耦合介导的。

DESCRIPTION (provided by applicant): Memory consolidation is the process by which the newly learned information, which exists in a labile state, becomes a long-lasting memory that is resistant to disruption. Long-term memory consolidation requires de novo protein synthesis, and it is very likely that dendritic protein synthesis is also involved in this process. Long-term potentiation (LTP) is a persistent increase in synaptic strength, and is considered a cellular correlate for long-term memory. Like memory consolidation, late forms of LTP (L-LTP) also require protein synthesis, and have been shown to specifically require dendritic protein synthesis as well as somatic protein synthesis. Memories of emotional experiences such as those produced in the fear conditioning-based inhibitory avoidance (IA) paradigm, are subject to modulation by various hormones. Noradrenaline is released from the locus coeruleus during arousal and enhances memory via beta-adrenergic receptors. The same is true in regards to LTP, which is likewise modulated by noradrenaline. Recent evidence from our laboratory and others suggest that astrocytes play a larger role in both learning and memory and LTP than previously thought. By contributing lactate to neurons through glycogenolysis and transfer via monocarboxylate transporters, astrocytes are critical to memory consolidation and LTP maintenance (see preliminary data). Interestingly, beta-adrenergic receptors are present on astrocytes and have also metabolic effects in astrocytes when stimulated. This project will test the contribution of astrocytes to long-term memory and LTP. Specifically, it will test the hypothesis that astrocytes critically contribute to memory formation by providing astrocytic-neuronal coupling through lactate that supports the high-energy demands associated with activation of dendritic protein synthesis. Furthermore, it will test the hypothesis that the noradrenergic-dependent modulation of memory is mediated by the astrocytic-neuronal coupling.