Cellular mechanisms of memory consolidation

记忆巩固的细胞机制

• 批准号: 246731133
• 负责人: Professor Matthew Larkum
• 金额: --
• 依托单位: Arbeitsgruppe Neuronale Plastizität
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/246731133?language=en
• 关键词: Cellular; mechanisms; memory; consolidation

Although the hippocampus has long been known to play a key role in learning and memory, long-term declarative memories (e.g. names and faces, facts about the world, etc.) are thought to reside in neocortex. It is therefore assumed that some, as yet unknown, processes occur in the interaction between the hippocampus and the neocortex that affect the influence of synaptic inputs to neocortical neurons. This process depends on the activity in the parahippocampal structures such as the entorhinal and perirhinal cortices through which the information from the hippocampus must go. There are several difficulties in investigating memory consolidation but one that is not often mentioned is the fact that connections to the neocortex coming from the parahippocampal structures target predominantly layer 1 (and parts of layer 2/3). This has the consequence that synapses most likely to be important to memory consolidation arrive at the distal tuft dendrites of cortical pyramidal neurons making them very hard to examine.In this project, we aim to investigate these synapses in vivo and in vitro using a range of methodologies that have been developed in our laboratory. We will use optogenetic tools to visualize and influence synaptic input to tuft dendrites from the entorhinal cortex. Using various dendritic recording methods (electrophysiological and imaging) we will examine the postsynaptic influence of these inputs on subthreshold and suprathreshold activity. Lastly, we will design a behavioural task for investigating these connections in the intact animal during and after learning.

虽然海马体在学习和记忆中起着关键作用，但长期的陈述性记忆（例如名字和面孔，关于世界的事实等）被认为存在于大脑皮层中因此，我们假设海马体和新皮层之间的相互作用中发生了一些未知的过程，这些过程影响了突触输入对新皮层神经元的影响。这个过程取决于海马旁结构的活动，例如来自海马的信息必须经过的内嗅和嗅周皮质。研究记忆巩固有几个困难，但不常提到的一个事实是，来自海马旁结构的新皮层连接主要针对第1层（以及第2/3层的部分）。这有一个后果，突触最有可能是重要的记忆巩固到达远端簇树突的皮质锥体神经元，使他们很难检查。在这个项目中，我们的目标是调查这些突触在体内和体外使用的一系列方法，已经在我们的实验室开发。我们将使用光遗传学工具来可视化和影响突触输入到来自内嗅皮层的簇状树突。使用各种树突记录方法（电生理和成像），我们将研究这些输入的阈下和阈上活动的突触后影响。最后，我们将设计一个行为任务，以调查这些连接在学习期间和之后的完整的动物。