The Role of Multi-innervated Dendritic Spines in Memory Formation in Ageing

老年时，大脑海马区的功能受损。这影响了新记忆的形成，我们相信它也会损害新获得的记忆的更新。随着年龄的增长，海马体中神经细胞的特性发生了变化，损害了神经细胞之间的交流。然而，由于新记忆的形成并没有在老年时完全消失，问题就出现了，什么机制解释了老年记忆的形成。我们最近发表在PNAS上的创新合作研究提出了这样一种机制。通过小鼠模型，我们首次证明了神经细胞之间的一种特殊连接的产生，即所谓的多神经支配的树突棘，在现有连接的加强受损时导致记忆的形成。我们最近的数据证实，这种远端神经回路中脊柱改变的比例效应，实际上补偿了突触损伤。涉及多神经支配的树突棘的记忆形成需要更多的训练，与依赖于加强现有连接的记忆形成相比，它的灵活性更低。我们的研究提出了一种假设，即老年记忆的形成取决于多神经支配的树突棘的产生，由于这种机制，记忆的形成速度减慢，新获得的记忆不那么灵活。在这里，我们将检验这个假设。我们将研究两种行为任务训练后的年轻成年小鼠和老年小鼠的海马体依赖记忆，并研究操纵对多神经支配树突棘产生的影响。

In old age the function of a brain region, the hippocampus, is compromised. This affects the making of new memories and we believe that it is also impairs the up-dating of newly acquired memories. With ageing the properties of nerve cells in the hippocampus change, impairing the communication between nerve cells. However, as the making of new memories is not fully abolished in old age, the question arises as to what mechanism accounts for memory making in old age. Our recent innovative collaborative study, published in PNAS, proposes such a mechanism. Using a mouse model, we have shown for the first time that the generation of a particular connection between nerve cells, so-called multi-innervated dendritic spines, leads to memory making when the strengthening of existing connections is impaired. This scaling effect of alterations of spines in distal neural circuits, in effect compensates for the synaptic impairments, which is confirmed by our recent data. The memory making that involves multi-innervated dendritic spines requires more training and it is less flexible in comparison to memory making relying on strengthening of existing connections. Our studies propose the hypothesis that in old age memory formation depends on the generation of multi-innervated dendritic spines and that because of this mechanism memory formation is slowed down and newly acquired memories are less flexible. Here, we will test this hypothesis. We will study hippocampus-dependent memory of young adult and aged mice after training in two behavioural tasks and we will investigate the impact of manipulations of the generation of multi-innervated dendritic spines.