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

在老年人的大脑区域，海马体的功能，是妥协。这会影响新记忆的形成，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变化，损害了神经细胞之间的交流。然而，由于新记忆的形成在老年时并没有完全消失，问题就出现了，什么机制解释了老年记忆的形成。我们最近在PNAS上发表的创新合作研究提出了这样一种机制。使用小鼠模型，我们首次证明了神经细胞之间特定连接的产生，即所谓的多神经支配树突棘，当现有连接的加强受损时，会导致记忆的形成。这种远端神经回路中棘的改变的缩放效应实际上补偿了突触损伤，这被我们最近的数据所证实。涉及多神经支配的树突棘的记忆制作需要更多的训练，与依赖于加强现有连接的记忆制作相比，它的灵活性较低。我们的研究提出了一个假设，即在老年记忆的形成取决于多神经支配的树突棘的产生，因为这种机制，记忆的形成减慢，新获得的记忆是不太灵活。在这里，我们将测试这个假设。我们将研究两个行为任务训练后的年轻成年和老年小鼠的大脑皮层依赖性记忆，我们将调查多神经支配的树突棘的产生的操作的影响。

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.