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MIT Study May Explain How Adult Brains Create New Memories

Millions of "silent synapses" in mature brains may help in new memory formation.


Neuroscience discoveries of the biological brain are important not only because they may lead to novel therapeutics to treat brain disorders, but also because they may serve as models for artificial intelligence (AI) machine learning. A new study by the Massachusetts Institute of Technology (MIT) shows that millions of silent synapses exist in adult brains—a discovery that may unlock how adults are able to continually learn and form new memories.

The neuroscientists who conducted this breakthrough discovery are lead author Dimitra Vardalaki, M.D., a Boehringer Ingelheim Fonds Ph.D. Fellow and MIT graduate student; senior author Mark T. Harnett, Ph.D., an Associate Professor in the Department of Brain and Cognitive Sciences and member of MIT’s McGovern Institute for Brain Research; and co-author Kwanghun Chung, Ph.D., an Associate Professor of Chemical Engineering and recipient of the Presidential Early Career Award for Scientists and Engineers.

Silent synapses are abundant in early development, during which they mediate circuit formation and refinement, but they are thought to be scarce in adulthood,” wrote the researchers at the Harnett Lab at MIT. “However, adults retain a capacity for neural plasticity and flexible learning that suggests that the formation of new connections is still prevalent.”

This new study demonstrates that roughly 30 percent of all synapses in the brain’s cortex of adult mice are silent, according to MIT.

Synapses are where the brain cells or neurons connect and communicate with each other. A single neuron can have between a few to hundreds of thousands of synaptic connections.

Neurons have a main body with strands. The transmitting neuron uses a thin strand called an axon to send signals. When an electrical signal or action potential passes down an axon, its tip releases a chemical signal called a neurotransmitter into the synapse. Depending on the neurotransmitter, the receiving neuron may activate an electrical charge to signal another neuron or not fire a charge. The receiving neuron can receive via its main body or tree-like branches called dendrites.

Prior to this discovery, scientists have theorized that in adult brains, synaptic plasticity is primarily due to variations in synaptic strength instead of introducing or removing individual synapses.

The discovery was made as part of a follow-on study, also conducted at Harnett’s lab, that showed that within an individual neuron, different types of dendrites receive information from distinct areas of the brain, and process signals in different ways before passing it to the body of the neuron. The researchers aimed to understand what would cause the differences in the behavior of dendrites by measuring neurotransmitter receptors in various dendritic branches.

By using a method developed by Chung called eMAP (epitope-preserving Magnified Analysis of the Proteome), the neuroscientists could get high-resolution images through the expansion and labeling of proteins in a tissue sample. During the imaging, they discovered that there were thin membrane protrusions extending from the dendrites called filopodia.

By applying eMAP to other parts of the adult brain of mice, the researchers found filopodia in various areas of the brain, including the visual cortex at markedly higher levels than has ever seen before.

These filopodia had neurotransmitter receptors that were missing AMPA receptors which are needed for synapses to pass along an electrical current. AMPA receptors are a type of glutamate receptors that mediate rapid excitatory synaptic transmission and play a key role in synaptic plasticity.

To test if the discovered filopodia are silent synapses, the neuroscientists deployed a modified patch-clamp method which involves administering a voltage through the cell membrane in order to measure the resulting current.

The neuroscientists discovered that the filopodia were silent synapses that could be activated by the combination of an electrical current from the body of the neuron with a glutamate release. Moreover, this conversion was easier than changing mature synapses according to the researchers.

“The synapses in the adult brain have a much higher threshold, presumably because you want those memories to be pretty resilient,” said Harnett in a statement. “You don’t want them constantly being overwritten. Filopodia, on the other hand, can be captured to form new memories.”

“This paper is, as far as I know, the first real evidence that this is how it actually works in a mammalian brain,” said Harnett in an MIT report.

This discovery may explain how adult mammalian brains can learn and form new memories through the activation of silent synapses without having to change existing synapses.

These results challenge the model that functional connectivity is largely fixed in the adult cortex and demonstrate a new mechanism for flexible control of synaptic wiring that expands the learning capabilities of the mature brain,” the MIT researchers concluded.

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