Dendritic Spines: How Memory Is Stored in the Brain

Over 100 years ago, Nobel Prize winner Ramon y Cajal first described structures called dendritic spines, located on the surface of brain cells. Since then, scientists have been trying to understand what dendritic spines are and how they function in the brain. Even with the latest technology, it is very difficult to research dendritic spines because they are so tiny—one dendritic spine is about 1/1,000 of a millimeter, and there are thousands of them on the surface of most nerve cells in the brain. Since dendritic spines can change shape and size quickly, some researchers have suggested that they are the structures in the brain where memories are created and stored. This hypothesis is based on hundreds of studies showing that forming a memory causes dendritic spines to undergo major changes in number, size, and shape. Likewise, preventing dendritic spines from changing may stop memories from forming. However, there is still a long way to go before we can identify exactly where memories are kept in the brain. Future studies may help us answer this fascinating riddle.


About
years ago, powerful microscopes were developed that allowed researchers to see brain cells called neurons in more detail.

NEURON
The elementary unit of the brain. It contains the receiving end (spines and dendrites), the transmitting end (axon) and the central part, the soma, which controls the activity of the whole unit.
At that time, the Spanish researcher Ramon y Cajal discovered that the membrane, or outer covering, of brain neurons was not as smooth as scientists previously thought it was. He discovered that brain neurons have thousands of tiny outgrowths, each about / , of a millimeter long, which are now called dendritic spines. For this work, Ramon y

DENDRITIC SPINE
A small structure opposite a presynaptic terminal (end) which receive input from the presynaptic cell, and controls the flow of information between the two cells.
Cajal won the Nobel Prize for Physiology or Medicine in .
Since then, we have learned a huge amount about dendritic spines. Most of what we know supports the idea that these spines are one of the main places in the brain where memories are created and stored [ ]. This article will explain, support, and expand on this hypothesis.

WHAT ARE DENDRITIC SPINES?
Let us begin by describing the parts of the dendritic spine. A dendritic spine looks like a mushroom ( Figure ), with a large head and a thin neck. The head is the place where two neurons connect and exchange information, an area called the synapse. neurons; and substances that control the number of receptors and their activity.

Figure
The structure of a neuron. substances in and out of the head. As a result of this regulation, the neuron changes the way it responds to stimuli.
According to one estimate, there are between -di erent types of substances that go in and out of dendritic spines through their necks, some in a very short amount of time. The movement of some of these substances can be controlled with molecular tools or with certain drugs. Controlling the passage of these substances may change the size and shape of the dendritic spine. It is also possible to control the dendritic spine's ability to send and receive electrical signals, which are one way that neurons communicate, but due the tiny size of dendritic spines, the methods we have today do not allow us to measure their electrical activities directly or reliably. This measurement problem makes it di cult for scientists to determine the neck's role in transmitting messages from the dendritic spine's head into the neuron.
Calcium is one important substance found in small amounts in dendritic spines. In addition to the many roles of calcium in the body, and especially in neurons, it is also responsible for activating enzymes ENZYME A protein produced by living cells that helps to start a chemical reaction or process.
(biological molecules that make reactions happen more easily) that initiate the transfer of messages from one neuron to another. There are sophisticated laboratory tools that allow us to precisely measure the amount of calcium in neurons and in their dendritic spines. These measurements can help us learn about how the head and the neck of the spine communicate, and can give us a fairly accurate picture of how dendritic spines change their shape and function.

ROLE OF DENDRITIC SPINES IN LEARNING AND MEMORY
The idea that dendritic spines are associated with learning and memory has been tested in a series of experiments that tracked changes in the structure of dendritic spines in the brains of laboratory rats and in brain slices. In these experiments, researchers looked at the spines before and after exposure to electrical stimulation. The electrical stimulation caused a phenomenon called long-term potentiation (LTP), which

LONG-TERM POTENTIATION (LTP)
Long-term amplification of an electrical signal along a brain neuron, which strengthens the connection between neighboring neurons. is expressed as an increase in responses of the neuron to electrical stimulation, and is generated along the dendritic tree (see Figure  ). Over the past years, LTP has been studied in thousands of experiments looking at the whole brain, brain slices, and brain cells grown in the lab. In a nutshell, these experiments showed that the brain uses an LTP-like mechanism to generate memory, and if this mechanism is disabled, the memory disappears or cannot be acquired. Our findings of LTP in dendritic spines following electrical stimulation thus tell us that spines assume an important role in synaptic plasticity. Likewise, a reduction in synaptic activity may lead to a process of Long-Term Depression (LTD), whereby dendritic spines that are not activated may shrink and lose their synaptic partner (e.g. Figure , bottom line).

Figure
Dendritic spines change following electrical stimulation. When researchers looked at a single dendritic spine as it was exposed to electrical stimulation, they discovered that, within a fraction of a

LONG-TERM DEPRESSION (LTD)
A condition opposite to LTP, whereby the connection between two neurons is weakened, leading to loss of connectivity and eventual loss of memory.
second, there is a massive flood of calcium ions into the spine. As a result, the head of the spine can swell up to -times its original size. Immediately after, there is a flow of neurotransmitters to receptors in the head of the spine, which increases the spine's response to the electrical stimulation ( Figure ). This change, at a later stage, in a process that lasts from minutes to hours, results in formation of new dendritic spines. These new spines cause a stronger connection between cells. In other words, in the brain, learning is based both on a change in the response strength of dendritic spines and on the creation of new spines. In this way, the connection between the cells that make up the memory in the neural network is tightened.

DENDRITIC SPINES IN AGING AND BRAIN DISEASES
Another path to understanding the relationship between learning and changes in dendritic spines is to look at how the spines change in an adult animal as it ages. As we know, as adult humans get older, memory gradually decreases. This process is not the same for everyone: some elderly people experience a sharp decline in memory, while others have only a moderate decline. This decrease in brain functions, including memory, is known as cognitive decline. A similar phenomenon also occurs in lab animals. Studies have identified a kids.frontiersin.org March | Volume | Article | Segal Dendritic Spine-Memory Storage correlation between cognitive decline and the number of dendritic spines in the brains of lab rats. That is, as rats' memory loss increases, the number of spines in their neurons also decreases. This does not mean that the decrease in the number of spines causes cognitive decline, but only that there is a positive correlation between the two observations. Further studies are required to confirm and fully understand these findings.
Another area in which there has been interesting progress in the study of dendritic spines is in the case of diseases of the nervous system. In one of the first studies on this topic, researchers examined neurons in the brains of patients with fragile X syndrome [ ], a disease that causes varying degrees of mental disability, autism, and communication disorders (among other things). It was found that the dendritic spines do not fully develop in the brains of people with this syndrome.
While these studies focus on understanding the relationship between brain disabilities and the structure of dendritic spines, they cannot explain the process that causes the disabilities. To fully understand the relationship between faulty dendritic spines and problems of brain function, we should be able to fix the problem, which we do not yet have [ ].

SUMMARY AND CONCLUSIONS
Understanding the structure and function of dendritic spines in the brain is very important, but also very challenging. First, the tiny size of dendritic spines makes them di cult to access, and in each neuron there are tens of thousands of such spines. Second, there are many kinds of dendritic spines, and it is not yet clear what the role of each type is. Beyond that, there is the big, unanswered question about the identity of the memory "unit" in the brain and how it works: Are memories held in a single dendritic spine, a single cell, or a group of cells connected to each other in a neural network? Researchers will only be able to answer this if they can locate a certain memory (say, of the letter A) in the brain; by damaging the dendritic spine/cell/neural network to see if only that specific memory is lost-not any other memory or function. If we can understand how the structure and function of an individual dendritic spine relates to the functioning of the entire brain, perhaps we will also be able to repair particular spines to restore memory and treat memory-related diseases such as Alzheimer's disease. Future generations of neuroscientists will face these challenges-maybe you will be one of them? . doi: . /frym. .

CONFLICT OF INTEREST:
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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THE N. YADLIN INTERDISCIPLINARY CAMPUS, RISHON LEZION, AGE:
We are a group of th grade students at the N. Yadlin Interdisciplinary Campus in Rishon Lezion. During the year we took part in the "Frontiers" course at school, where we learned with the help of Frontiers articles (also in English); Made videos and posters; Researched di erent fields of science, and even reviewed some articles. We are curious, critical and love science and challenges.

MEITAL, AGE:
Proud nerd, lives in Petah Tikvah. I started reading at the age of three, and to my great pride I still have not stopped. I am a Potterhead (hard fan of Harry Potter), and I have been a nerd for half my life. I started studying for a degree in psychology! At the age of five, I read parenting books to understand how adults perceive me as a human being, and why my kindergarten friends and I do what we do. I am an older sister and love to draw. When I grow up, I want to be like my cousin, or a dinosaur, but only because the dinosaurs are extinct.

MENAHEM SEGAL
Menahem Segal was born in Tel Aviv in . He studied at Bar Ilan University, where he earned his bachelor's and master's degrees. He traveled with his young family to do his doctoral studies in brain research at the California Institute of Technology. Upon his return to Israel, he joined the faculty of the Weizmann Institute of Science. Today, seven years post retirement, he continues to study nerve cells as professor emeritus at the Weizmann Institute. He rides a motorcycle for the past years without a severe accident. He was last seen in the skies over our country, as shown in the photo. *menahem.segal@weizmann.ac.il