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

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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.