The brain must store memories to learn and acquire knowledge, but where do these memories go, and what do they look like? Finally, scientists have some answers.

In the early 20th century, the German scientist Richard Semon, a memory researcher and evolutionary biologist, coined the term "engram" for the physical substrate of a memory. Scientists have been looking for them ever since.

"Where are the engrams? This was one of the questions we asked," Peter Jonas, neuroscientist at the Institute of Science and Technology in Austria, said in a news release.

"Synaptic plasticity, the strengthening of communication between neurons, explains memory formation at the subcellular level," Jonas said. "To find the engram, we, therefore, explored structural correlates of synaptic plasticity."

Jonas and his colleagues precisely measured the activity of single synapses inside the hippocampus, the region of the brain responsible for learning and memory. Inside the hippocampus, pyramidal cells are linked with granule cells by synapses.

"We made simultaneous recordings of electrical signals from a small pre-synaptic terminal and its postsynaptic target neuron," said IST postdoctoral researcher David Vandael. "This is the perfect way to examine the synapse."

The observations showed that when a granule cell fires, it triggers a kind of plasticity called post-tetanic potentiation, which boosts the link between the granule and pyramidal cell for a few minutes.

Scientists hypothesized that plasticity arises when heightened neuronal activity primes vesicles to release neurotransmitters. Vesicles are cellular components that facilitate the uptake and release of communicative molecules.

"Instead, we found that after a granule cell is active, more vesicles containing neurotransmitter are stored at the pre-synaptic terminal," Vandael said. "Firing patterns induce plasticity through an increase of vesicles in this active zone, which can be stored for a few minutes."

In other words, plasticity allows for storage, not necessarily the release of neurotransmitters.

The new research showed that during learning, when granule cells are more active, vesicles flood the active zone. When activity tapers, these vesicles remain, and when activity picks back up, the vesicles are ready and in position to release neurotransmitters into the synapse.

"Short-term memory might be activity stored as vesicles that are released later," Vandael said.

It's possible, scientists surmise, that the activity observed by the IST research team -- and detailed Tuesday in the journal Neuron -- is, in fact, the elusive engram.

"By analyzing the biophysical and structural components of plasticity, David may have discovered the engram -- if we believe that synaptic plasticity underlies learning," Vandael said.

"It is fascinating to think of memories as numbers of neurotransmitter-containing quanta, and we truly believe it will be inspiring for the neuroscience research community," Vandael said. "We hope our work will contribute to solving part of the unresolved mysteries of learning and memory."

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