Adult mouse brains have ‘silent synapses’.

Learning lots of new information as a baby requires a pool of preparation to be released, the immature connections between nerve cells to quickly form memories. Called silent synapses, these connections are inactive until called upon to help make memories, and were thought to be particularly present in the developing brain and die out over time. But a new study reveals that many synapses are silent in the adult mouse brain, researchers report Nov. 30 nature.

Neuroscientists have long been puzzled as to how the adult human brain can hold stable, long-term memories while simultaneously maintaining a certain flexibility to make new memories, a concept known as plasticity.SN: 7/27/12). These silent synapses may be part of the response, says Jesper Sjöström, a neuroscientist at McGill University in Montreal, who was not involved in the study.

“Silent synapses are ready to sickle up,” he says, perhaps making it easier to store new memories as an adult using these connections by not having mature synapses to delete or destabilize already connected memories. “That means there is much more room for complete plasticity in the brain than we previously thought.”

In a previous study, neuroscientist Mark Harnett of MIT and his colleagues had altered many of the long, rod-shaped structures called filopodia in the adult mouse brain. That surprised Harnett because these extrusions are usually found in nerve cells in the developing brain.

“Here they were in full-grown animals, and we could see them clearly in the liquid,” says Harnett. So he and his team decided to investigate what role filopodia play, and if they might silence synapses.

The researchers used a technique to enlarge the brains of adult mice combined with high-resolution microscopy. Since the nerve cell connections and the molecules called receptors that allow communication between the connected cells are so small, these synapses have been revealed by methods that past research has missed.

The team looked for the typical signs of a silent synapse: the presence of a type of receptor called NMDA and the absence of others known as AMPA receptors. Both types of receptors respond to the chemical messenger glutamate, but both typically need to be present for the synapse to be active.

Of the more than 2,000 synapses that the team looked at, about 30 percent were filopodia, and of those, almost all had characteristics suggesting that synapses can be silent.

To test whether the hosts were truly silent, the researchers turned to glutamate. The artificially added chemical messenger was not enough to activate the synapses, the team found, suggesting that the connections were actually silent.

Adding an electrical current in addition to glutamate converts these connections from immature to mature synapses. This also happens in the developing brain, when a new memory is formed from a silent synapse.

It is unclear whether silent synapses also prevail in the adult human brain, although Harnett and Sjöström’s other scientists think it is unlikely. Researchers are now using the same techniques in human brains to find out.

Finding silent synapses in adult human brains could have implications for treating conditions like drug addiction. Research on developing mice given cocaine suggests that drug use generates more silent synapses, which may then play a role in relieving symptoms. If scientists develop a way to control the number of silent synapses, they can target conditions that show abnormal levels of synapse silence.

What’s clear is that silencing synapses probably reflects how the adult brain balances old memories while making new ones, Harnett says. By doing this, “it becomes much easier to pay off the trade-off all of a sudden”.