Astrocytic-neuronal mechanisms in memory formation and cognitive impairments

描述(申请人提供)：保持和促进健康的认知功能，其中记忆是最重要的之一，是心理健康研究的主要目标之一。识别长期记忆形成的机制和有助于预防或治疗记忆损害的靶点是心理健康的一个重要目标。到目前为止，对包括记忆在内的认知功能的机制的研究主要集中在阐明神经元和神经元网络的贡献上。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。人们对这些星形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可能参与记忆和认知障碍的研究也知之甚少。利用大鼠的情景恐惧条件记忆任务，我们最近发现了依赖星形胶质细胞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，据我们所知，在哺乳动物的大脑中，星形胶质细胞在长期记忆的形成中扮演着必要和积极的角色。这一建议旨在进一步研究星形胶质细胞的生物学机制及其在长期记忆形成和伴随应激相关认知障碍的记忆损害中与神经元的相互作用。重要的是，将研究早期发育和成年期记忆形成的潜在机制，以确定相似和不同之处。这些研究的结果应该会促进我们对记忆形成的生物学机制的了解，并应该导致理解认知功能和预防或逆转与应激相关的认知障碍相关的认知障碍的新假说和工具。

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.