Astrocytic-neuronal mechanisms in memory formation and cognitive impairments

描述（由申请人提供）：维持和促进健康的认知功能，其中记忆是最重要的一个，是心理健康研究的主要目标之一。确定长期记忆形成的机制和有助于预防或治疗记忆障碍的目标是心理健康的一个重要目标。到目前为止，包括记忆在内的认知功能机制的研究主要集中在阐明神经元和神经元网络的贡献。然而，最近几十年的研究结果表明，星形胶质细胞积极参与突触功能的调节，包括长期可塑性和记忆。关于这些星形胶质细胞机制的性质和功能知之甚少。此外，关于星形胶质细胞功能在记忆和认知障碍中的可能参与也知之甚少。最近，我们在大鼠中使用情境恐惧条件记忆任务，确定了星形胶质细胞依赖的代谢偶联与神经元在大鼠长期记忆形成中的关键作用。这些发现首次表明，在哺乳动物大脑中，星形胶质细胞在长期记忆形成中发挥着必要和积极的作用。该提案旨在进一步研究星形胶质细胞的生物学机制及其与神经元在长期记忆形成和伴随压力相关认知障碍的记忆障碍中的相互作用。重要的是，在早期发展和成年期的记忆形成的机制将被调查，以确定相似性和差异。这些研究的结果应该推进我们对记忆形成的生物学机制的认识，并应该导致新的假设和工具来理解认知功能，预防或逆转与压力相关的认知障碍有关的认知障碍。

DESCRIPTION (provided by applicant): Maintaining and promoting healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Identifying mechanisms of long-term memory formation and targets that help in preventing or treating memory impairments is an important goal in mental health. Thus far, the studies of mechanisms underlying cognitive functions including memory have mainly focused on elucidating the contribution of neurons and neuronal networks. However, findings of the last few decades indicate that astrocytes actively participate in the regulation of synaptic functions including long-term plasticity and memory. Very little is known about the nature and functions of these astrocytic mechanisms. Furthermore, very little is known also about possible involvement of astrocytic functions in memory and cognitive impairments. Using a contextual fear conditioning memory task in rats we have recently identified a critical role of astrocytes- dependent metabolic coupling with neurons in long-term memory formation in rats. These findings show, for the first time to our knowledge, that, in a mammalian brain, astrocytes play a necessary and active role in long-term memory formation. This proposal aims at further investigating the biological mechanisms of astrocytes and their interactions with neurons in long-term memory formation and in memory impairments that accompany stress-related cognitive impairments. Importantly, mechanisms underlying memory formation during early development and in adulthood will be investigated to determine similarities and differences. Results from these studies should advance our knowledge of the biological mechanisms underlying memory formation and should lead to novel hypotheses and tools for understanding cognitive functions and preventing or reversing cognitive impairments linked to stress-related cognitive disorders.