How does the Brain Preserve Long-term Memory

The brain safely preserves our precious memories, from sweet first kisses to the birth of a baby. How is this mystery feat possible, and how does it work?

Neuroscientists at Columbia University have succeeded in uncovering the molecular machinery that allows the brain to maintain this type of long-term memory in a new study using laboratory mouse cells.

The team looked at the activity of  neurons in the brain, and found how certain proteins (CPEB3) prepare neurons to store memories over time.

The study, published today in the National Academy of Sciences (PNAS), presents a whole new view of one of the brain’s most common and fundamental molecular functions. It also suggested new targets for the treatment of neurodegenerative disorders characterized by memory loss, such as Alzheimer’s disease.

“Memory is the foundation of existence”

Professor Eric Kandel (Co-Director of Brain Science and Columbia Motimer Zuckerman Mind Brain Behavior Research Institute), who won the Nobel Prize in Physiological Medicine in 2000 for the molecular basics of memory, said, It creates an identity and permeates our lives and becomes the basis of our existence. ”

But “memory is a biological process at its core that is no different from a heartbeat, and we’ve relighted the molecular foundations behind the brain’s ability to create, preserve, and recall memories in our lives.” .

All memories, even fleeting memories, are made when small branches, called axons, that extend from neurons are connected.

These junctions, called synapses, can be as strong or weak as shaking hands. If the connection is weak, the memory may disappear. Conversely, if strong, it can last long.

In normal brain activity, neurons generate electrical signals that travel along an axon. When the electrical signal reaches a junction called a synapse, neurotransmitters are released. These neurotransmitters bind to receptors on other cells and change their electrical activity. In memory, CPEB3 produced in the neuronal centrosomes of the hippocampus travels along the axons and is released at synapses, helping to create and maintain memory.

In normal brain activity, neurons generate electrical signals that travel along an axon. When the electrical signal reaches a junction called a synapse, neurotransmitters are released. These neurotransmitters bind to receptors on other cells and change their electrical activity. In memory, CPEB3 produced in the neuronal centrosomes of the hippocampus travels along the axons and is released at synapses, helping to create and maintain memory.

Memory Loss Without CPEB3 Protein

The researchers recently reported that enhancing synapses results in observable changes anatomically.

In 2015, Dr. Candle’s team identified rats with a protein called CPEB3 that plays a key role in this anatomical change. They found that CPEB3 is present at the brain’s synapses when memories are formed and recalled.

When the team interfered with the production of CPEB3 in mice, they formed new memories but did not retain them.

Co-Senior author, Luana Fioriti (Principal Researcher at the Mario Negri Institute of Pharmacy, Milan, Italy) said, “Without CPEB3, synaptic connections were lost and memory disappeared.” Discovering the function was the driving force behind the research. ”

Memory creation and stabilization

CPEB3 is produced at regular intervals in the center of neurons in the hippocampus, the brain’s memory center. The team found that once CPEB3 is produced, it is transferred to processing bodies (P-bodies), which are separate chambers that are ready to go to sleep and ready for use.

Co-first author, Dr. Lenzie Ford, Ph.D., Professor of Candles, said, “P has no physical barriers such as cell membranes that can contain CPEB3.” By sticking the P bodies together, it creates a kind of biophysical force field that allows CPEB3 to stay inside rather than escape to other parts of the cell. ”

Once P is filled with dormant CPEB3, it leaves the center of the neuron and moves along the nerve branch to the synapse. When the animal experiences something and begins to form memory, P is dissolved and CPEB3 is released to the synapse to help create memory.

Over time, as more CPEB3 is released, these synapses strengthen. This changes the anatomical state of the neuron and as a result the memory is stabilized.

 

“Promising Target for Neurodegenerative Diseases”

“The results of this study emphasize that protein synthesis plays a central role in memory retention,” Candle said.

“There may be additional processes that we haven’t discovered yet, but this study integrates state-of-the-art biochemistry, genetics, and microscopy tools, unparalleled detail, revealing the wonderful biological mechanisms of memory,” he said.

In addition to revealing memory, the study also provides insights into neurodegenerative disorders characterized by memory loss.

Because the importance of CPEB3 in memory storage has been demonstrated and there is a version of CPEB3 in the human brain, the team sees this protein as a promising area of ​​interest in the treatment of neurodegenerative diseases.

“The science of how synapses are formed and how they’re strengthened over time is important for the detoxification and dying of memory-related synapses, such as Alzheimer’s,” Fiority said.

“By continuing to build this understanding of memory, we hope to one day develop a useful way to boost CPEB3 to prevent synaptic degeneration and slow memory loss,” he said.

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