Where are memories stored in the brain? Research suggests they may be in the connection between cells

All memory storage devices, from your brain to the RAM in your computer, store information by varying their physical quality. More than 130 years ago, the pioneering neuroscientist Santiago Ramon y Cajal first proposed that the brain stores information by rearranging connections, or synapses, between neurons.

Since then, neuroscientists have been trying to understand the physical changes involved in memory formation. But visualizing and mapping synapses is a tricky business. For one, synapses are very small and tightly packed together. They are roughly 10 billion times smaller than the smallest object that a standard clinical MRI can visualize. Furthermore, there are about 1 billion synapses in rat brains that researchers often use to study brain function, and they are all opaque to translucent in color, like the tissues around them.

ONE new imaging technique My colleagues and me however developed has allowed us to map the synapses during memory formation. We found that the process of forming new memories changes the way brain cells connect with each other. While some areas of the brain made more connections, others lost them.

Mapping new memories in fish

Previously, researchers focused on record electrical signals produced by nerve cells. Although these studies confirmed that neurons change their response to specific stimuli after memory is formed, they were unable to determine what drives those changes.

To study the physical changes of the brain as it forms a new memory, we created a 3D map of zebrafish synapses before and after memory formation. We chose zebrafish are our test subjects because they are large enough to have a functioning human brain, but small and transparent enough to provide a window into a living brain.

Black and white image of zebrafish larvae.
The zebrafish is an especially suitable model for neuroscience research. Zhuowei Du and Don B. Arnold, CC BY-NC-ND

To create a new memory for fish, we used a type of learning process called conditional reaction. This involves exposing the animal to two different types of stimuli simultaneously: a neutral one that does not react and an unpleasant stimulus that the animal tries to avoid. When these two stimuli were combined for sufficient time, animals responded to the neutral stimulus as if it were the unpleasant stimulus, indicating that it produced a associative memory tie these stimuli together.

As an unpleasant stimulus, we gently heat the fish head with an infrared laser. When the fish wags its tail, we take it as a sign that it wants to escape. When the fish is exposed to a neutral stimulus, the light comes on, the tail blinking means it is remembering what happened when it previously encountered the unpleasant stimulus.

Diagram illustrating the classic behavior of a dog salivating in response to a bell.
Pavlov’s dog is the most famous example of the classical conditioning, in which a dog salivates in response to the sound of a bell because it has formed an associative memory between the sound of the bell and the food. Lili Chin / Flickr, CC BY-NC-ND

To generate the maps, we genetically engineered zebrafish with neurons that produce fluorescent proteins that bind to synapses and make them visible. We then image the synapses with a custom-built microscope that uses a much lower dose of laser light than standard devices that also use fluorescence to produce images. Because our microscope causes less damage to nerve cells, we can image synapses without losing their structure and function.

Image of neurons in bright red in a live fish brain, with synapses in green
This image shows neurons in a live fish brain, with synapses colored green. Zhuowei Du and Don B. Arnold, CC BY-NC-ND

When we compared 3D synaptic maps before and after memory formation, we found that neurons in one brain region, the anterolateral striatum, developed new synapses in the brain. when neurons mainly in the second region, the anterior sternal region, lose their synapses. This means that new neurons are pairing with each other, while others destroy their connections. Previous tests have suggested that back pallium of fish may be similar to the amygdala of mammals, which store fear memories.

Surprisingly, the changes in the strength of existing connections between neurons that occur with memory formation are very small and indistinguishable from those in amorphous control fish. new memories. This means that associative memory formation involves synapse formation and loss, but does not necessarily change the strength of existing synapses, as was previously thought.

Researchers from the Howard Hughes Medical Institute captured video of a baby zebrafish’s active neurons as it sees things and tries to move.

Can synaptic deletion erase memories?

Our new method of observing brain cell function could open the door not only to a deeper understanding of how memory actually works, but also potential avenues for the treatment of neuropsychiatric diseases such as PTSD and addiction.

Related memories tend to be much stronger than other types of memories, such as conscious memories of what you ate for lunch yesterday. Furthermore, related memories are generated by classical conditioning, which is said to be similar to traumatic memories cause PTSD. On the other hand, harmless stimuli similar to what someone experienced at the time of trauma can trigger recall of traumatic memories. For example, a bright light or a loud noise can bring back memories of combat. Our study reveals the role synaptic connections may play in memory and may explain why associative memories can last longer and be remembered more vividly than other types of memories. other breast.

Currently, the most common treatment for PTSD, Exposure therapy, which involves repeatedly exposing the patient to a harmless but inducing stimulus to prevent recall of the traumatic event. In theory, this indirectly restructures the brain’s synapses to make memory less painful. Although some success has been achieved with exposure therapy, patients prone to relapse. This suggests that the underlying memory that causes the traumatic response has not yet been eliminated.

Conceptually tied to classical conditioning, prolonged exposure therapy is one way to treat PTSD.

It remains unclear whether synaptic creation and loss actually promotes memory formation. My Lab has developed technology that can quickly and accurately remove synapses without damaging nerve cells. We plan to use the same methods for synaptic removal in zebrafish or mice to see if this alters associative memories.

It is possible to physically erase the relevant memories that underlie devastating conditions such as PTSD and addiction with these methods. Before such treatment can even be contemplated, however, changes in the synapse encoding the associated memories need to be more precisely defined. And it is clear that there are serious ethical and technical obstacles that need to be addressed. Still, it’s tempting to imagine a distant future in which arthroscopic surgery can erase bad memories.

Don Arnold, Professor of Biological Sciences and Biomedical Engineering, USC Dornsife College of Letters, Arts and Sciences

This article was republished from Conversation under a Creative Commons license. Where are memories stored in the brain? Research suggests they may be in the connection between cells

Caroline Bleakley

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