More than half of hippocampal synapses vanish, yet mouse memories remain intact

How do we remember the distant past? For decades, scientists have believed synaptic potentiation—the adaptive strengthening of our brain's cellular connections—to be the key to memory retention. Researchers from the Okinawa ...

Their new paper, published in Science , demonstrates the importance of higher-order synaptic architecture, suggesting that specific clustered patterns of connections between brain cells may be key to retaining long-term memory. Professor Kazumasa Tanaka, head of OIST's Memory Research Unit, says, "Previously, synaptic strengthening was thought to be key to memory recall, and that stronger synapses with larger dendritic spines were fundamental to long-term memory retention. Here, we show that not every synapse matters and demonstrate instead the vital importance of engram architecture. The study indicates that small clusters of engram-engram synapses are preserved to enable accurate recall even after hibernation."

The physical forms of memories Much like computer storage, humans require a physical memory trace to be stored in the brain. This physical trace, known as an engram, is encoded through a dedicated network of brain cells undergoing changes at their synapses, the junctions where they meet. When connecting brain cells repeatedly fire together, their synapses strengthen, increasing neurotransmitter release and triggering structural changes, such as larger dendritic spines, which expand the contact area between the two cells. Conversely, when a particular connection isn't very active, the synaptic bonds between the cells weaken and may eventually disappear altogether.

An illustration of the inner workings of a mouse brain during artificial hibernation. Workers prune the irrelevant dendritic spines from brain cells, leaving only the synapses necessary for long-term memory retention. Credit: Luo-chu Yang Read more

Shown on the left is a typical synapse, where one brain cell connects to another (the axon of one connecting to the dendrites of the other cell). Each dendrite is covered in tiny protrusions known as dendritic spines, which house receptors for neurotransmitters, chemical messengers that transmit signals between cells. Electrical signals in the axon trigger the release of these neurotransmitters across the synapse. When a particular synapse is very active, it can lead to physical changes such as more neurotransmitter release and larger dendritic spines with a higher density of receptors. The opposite can also occur if a connection isn't very active for a long time; fewer neurotransmitters will be released, and dendritic spines can shrink or even disappear. Credit: Luo-Chu Yang Read more

This diagram shows two characteristic patterns found within the study. On the left, we see a multi-synaptic bouton (MSB), where one presynaptic terminal joins to multiple different dendritic spines on different cells. The researchers found that MSBs were more likely to be conserved following hibernation, suggesting their essential role in memory retention. On the right, we see clustered engram patterns. Dendritic spines that are close together but that connect to various axons of neurons in a different section of the brain are active within the same engram. Again, the researchers found that clustered engram synapses were preferentially conserved after artificial hibernation, which suggests their importance in memory retention. Credit: Luo-chu Yang Read more