Cellular mechanisms underlying short-term memory in the hippocampal CA1 region

海马 CA1 区短期记忆的细胞机制

• 批准号: 250031998
• 负责人: Professor Dr. Motoharu Yoshida
• 金额: --
• 依托单位: Leibniz-Institut für Neurobiologie (LIN)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/250031998?language=en
• 关键词: Cellular; mechanisms; underlying; short; term

Short-term memory is a cognitive function which enables us to mentally retain information for short periods of time (up to tens of seconds). It is required in daily life in order to understand speech, make decisions, solve problems, and perform many other cognitive functions. Understanding cellular mechanisms and molecular correlates of short-term memory is, therefore, of great importance for maintaining or improving quality of life in neurodegenerative disorders, as well as during natural aging processes in which short-term memory function declines. Classically, it has been believed that sustained spiking activity of neurons (persistent firing) supported by synaptic network maintains information as short-term memory. In contrast, we, and others, have established the involvement of transient receptor potential canonical (TRPC) channels in persistent firing in individual neurons, independent of the synaptic network. However, these studies were limited to in vitro experiments, and for many years it remained unclear whether TRPC channels could support in vivo persistent firing and short term memory performance. More recently, however, the role of TRPC channels in short-term memory and in vivo neural activity has been demonstrated by us, among others, in mice, indicating that TRPC channels may be a key mechanism of short-term memory. In this project, we further clarify the specific role of TRPC channels by resolving the current controversy and by extending our understanding of the role of TRPC channels in vivo in the hippocampus. First, the observation of intact persistent firing in TRPC knock-out mice challenges the role of TRPC channels in persistent firing in individual neurons. We aim to resolve this issue by combining genetic and pharmacological manipulations in vitro. Second, the roles of TRPC channels in neural activity in vivo still remain largely unknown. Therefore, we will conduct in vivo electrophysiological recordings in order to investigate the effect of TRPC channel manipulations on persistent firing and other memory related activity. These experiments will provide insights into the core mechanism of persistent firing and short-term memory, and into cognitive deficits due to aging or pathology.

短期记忆是一种认知功能，它使我们能够在短时间内（长达数十秒）在精神上保留信息。日常生活中需要它来理解言语，做出决定，解决问题，以及执行许多其他认知功能。因此，了解短期记忆的细胞机制和分子相关性对于维持或改善神经退行性疾病的生活质量以及在短期记忆功能下降的自然衰老过程中非常重要。 传统上，人们认为突触网络支持的神经元的持续尖峰活动（持续放电）维持信息作为短期记忆。相反，我们和其他人已经建立了瞬时受体电位典型（TRPC）通道参与个体神经元的持续放电，独立于突触网络。然而，这些研究仅限于体外实验，并且多年来仍不清楚TRPC通道是否可以支持体内持续放电和短期记忆性能。然而，最近，TRPC通道在短期记忆和体内神经活动中的作用已经被我们证明，其中包括在小鼠中，表明TRPC通道可能是短期记忆的关键机制。 在这个项目中，我们进一步澄清TRPC通道的具体作用，解决目前的争议，并通过扩展我们的理解TRPC通道在体内海马的作用。首先，在TRPC敲除小鼠中观察到完整的持续放电挑战了TRPC通道在个体神经元中持续放电的作用。我们的目标是解决这个问题相结合的遗传和药理学操作在体外。其次，TRPC通道在体内神经活动中的作用仍然很大程度上未知。因此，我们将在体内进行电生理记录，以研究TRPC通道操作对持续放电和其他记忆相关活动的影响。 这些实验将为持续放电和短期记忆的核心机制以及由于衰老或病理学导致的认知缺陷提供见解。