From birth to old age - How our brain transforms through life

Pruning, reorganization, connectivity, and degeneration - how does our brain change throughout life, and how does this affect our functioning?  

Rotem Mika/ Weizmann Institute of Science|
The human brain undergoes numerous transformations from birth to death. Some are subtle and routine, such as those occurring when we acquire new skills or form memories. Others are more substantial, significantly impacting the brain’s structure and function - and consequently, our character and behavior.
The human brain is a large collection of nerve cells, surrounded and interspersed with various types of supportive cells known as Glial cells. Nerve cells are specialized in receiving and processing sensory information, and quickly relaying it to other nerve cells or organs, such as muscles and glands, to initiate actions.
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The brain
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An adult human brain contains approximately 86 billion nerve cells that communicate with each other through intercellular junctions called synapses. At each synapse, one side is the transmitting nerve cell, and the other is the receiving cell, which integrates incoming signals from multiple sources. The cumulative input of these signals determines whether the receiving cell will be activated and will propagate the neural signal forward.
When a nerve cell is activated, either in direct response to a sensory stimulus or in response to signals received from other nerve cells, its electric potential changes. This change in electric potential generates an electric signal that travels along the cell's tail, called the axon, and reaches the terminal at its end. In response, the terminal releases molecules of neurotransmitters - a group of substances used for communication between nerve cells - which cross the synapse and bind to receptors on the surface of the receiving cell. The intensity of the activation and the nature of the connection between the two cells determine whether the signal will be transmitted forward.

From birth to adulthood - Major changes in the brain

All of our brains are fundamentally similar, especially during the early stages of our lives. Generally, each region of the brain has defined roles. That is, innate patterns of connectivity between different brain areas are naturally established from birth. During pregnancy, the first nerve cells that form in the developing fetus navigate toward the nerve cells that will become their target connections, guided by chemical signals that direct their path.
All of this is true regarding the basic development of brain tissues. However, the transformations that occur next, particularly after birth, are highly individual, akin to a fingerprint. These changes include variations in the number of nerve cells, their efficiency, the number of synaptic connections, and the strength of these connections. For example, infants have significantly more nerve cells and an abundance of synapses compared to adults.
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This abundance of neurons and synapses enables infants to absorb vast amounts of information and quickly learn the languages and cultural codes they are exposed. Early learning, particularly during the initial stages of life, is therefore crucial. At this stage, infants are in an information-gathering phase, but their ability to process information deeply is still developing. To refine this processing ability, the brain eliminates excess nerve cells and optimizes the efficiency of the remaining ones. This involves structural improvements in the synapses connecting nerve cells.
Another transformation that begins in the early years of life and continues until adulthood is myelination, a process that significantly enhances neural signal transmission. During myelination, cells undergo a gradual transformation which optimizes their functioning, while supporting cells form an insulating layer around the axon, the long “tail” of the nerve cell. This insulation, composed of a fatty white substance called myelin, wraps around the axon, facilitating the rapid conduction of electrical signals, which often need to travel long distances along the axon.
The number of cells and the extent of connections between them do not necessarily reflect the efficiency of brain processes. Increased efficiency is often linked to a reduction in the number of cells and connections. Around the age of two, and continuing throughout childhood, the brain undergoes a process called "synaptic pruning," which significantly reshapes its structure and function. During this process, excess connections and cells that we are born with are refined and their quantity is reduced, forming the stable structure of the adult brain.
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This process includes programmed cell death and the deliberate elimination of synapses, reducing the number of brain cells by about 15% and the connections between nerve cells by a similar proportion, allowing the brain to mature. During childhood, competition for resources takes place in the brain, and cells that manage to form meaningful connections are rewarded and survive. In essence, only the active connections remain. In essence, this means that the active connections are the ones that survive.
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Synaptic pruning occurs in stages. Initially, it is observed in brain areas responsible for sensory processing, as children absorb increasing amounts of information and refine their sensory abilities. In contrast, regions of the brain associated with complex thinking and decision-making mature only towards the end of adolescence. During this stage, the prefrontal cortex undergoes significant remodeling. This brain region, which plays a role in emotional regulation and is part of the brain's reward system, is associated with the pursuit of gratification. Synaptic pruning in the prefrontal cortex constitutes a reduction of roughly 50% in the amount of synapses in this region. This may explain certain behavior changes associated with adolescence, such as risk-taking and thrill-seeking.
Synaptic pruning occurs in stages. It begins in brain areas responsible for sensory processing, as children absorb vast amounts of information and sharpen their sensory abilities. In contrast, regions associated with complex thinking and decision-making mature much later, towards the end of adolescence. During this period, the prefrontal cortex undergoes significant remodeling. This region, crucial for emotional regulation and part of the brain's reward system, is linked to the pursuit of gratification. Synaptic pruning in the prefrontal cortex results in a reduction of roughly 50% in the number of synapses, which may help explain behavioral changes common in adolescence, such as increased risk-taking and thrill-seeking.
In a study conducted in the late 1970s researchers measured the number of synapses in the brains of 21 individuals who died at various ages - from newborns to people in their 90s. Examination of the prefrontal cortex revealed that synaptic density immediately after birth was similar to that of adults, but the synapses appeared different. At the beginning of life t, they were small and thin, described by the researchers as “immature”. It was also found that the number of synapses increased rapidly after birth, peaking during the second year of life, followed by a decline, especially during adolescence. During adulthood, the number of synapses remains relatively stable, with only a slight decline in old age. It is important to note that this does not imply that the adult brain does not change, but rather that the changes are more subtle and gradual.

Adulthood - Subtle changes

At every age, the connections between nerve cells influence the way we think. Some of these connections represent specific memories, concepts, and pieces of information. Throughout our lives, new connections between nerve cells are formed with every instance of learning. These connections are flexible and constantly subject to change. The connection between two nerve cells can strengthen or weaken depending on circumstances, a functional flexibility known as synaptic plasticity.
Strengthening or weakening the connection between two nerve cells—a synapse—manifests as changes in its characteristics. For example, the nerve cell transmitting the neural signal might release a greater or smaller amount of neurotransmitters, or the number of receptors on the receiving cell might increase or decrease. When a synapse strengthens, more neurotransmitters are released into it, binding to more receptors on the receiving end, thereby increasing the likelihood of generating an electrical signal to carry the neural message forward.
Changes in synaptic characteristics have a significant impact on us. For example, in the context of memory, weakened or loosened synapses correspond to forgetting. Every time we repeat an action, we reinforce the connections between the neurons involved, making the action easier to remember. This mechanism allows us to influence what happens in our brains, choosing which connections to strengthen. For example, mastering a particular skill requires repeated practice, reinforcing the neural connections involved in that activity.
Memories can also change, through a process called re-consolidation. When we retrieve a memory, it becomes somewhat malleable and open to modification. This allows memories to be updated, incorporating new associations, while sometimes they may even undergo significant rewriting that alters their content. Studies conducted on rats demonstrated that interfering with the process of re-consolidation during memory retrieval can weaken memories.
This ability is very significant when dealing with trauma, as it enables the reprocessing of traumatic memories. Beyond manipulations that are made possible by re-consolidation, such as implanting or weakening memories, re-consolidation also has everyday significance, enabling flexibility and adaptation whenever we retrieve a piece of information. For example, if we’ve learned that chocolate is brown or white and then encounter a new pink chocolate variety we can update our understanding to recognize three possible colors of chocolate.
In addition to alterations in the number of synapses and their structure, we know today that new nerve cells are also formed in our brains throughout life. This process of new nerve cell formation, called neurogenesis, occurs in a limited and localized manner but has been identified to take place in the hippocampus, a brain region central to memory formation, retrieval, and learning. While the role of neurogenesis in human learning is not fully understood, studies have shown that in its absence rats have difficulties in learning new things.
Thus, in adulthood, the primary driver of brain changes is learning. Through learning, continuous processes of transformation occur, reflected in the number of synapses, their characteristics, and also in the formation of new cells.

Aging - Risk of degeneration

What happens to our brains as we age? As previously stated, in the 1970s researchers found that starting around the age of 74 a decline in the number of neural connections in the brain becomes apparent. However, more recent findings paint a different picture. For instance, a study published in recent years measured the density of connection between nerve cells using positron emission tomography (PET) - a non-invasive imaging technique that enables observation of rapid processes in the body, such as those occurring during cellular metabolism. The researchers found no significant change in the number of synapses between the ages of 18 and 85.
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Nevertheless, aging remains the primary risk factor for most neurodegenerative diseases. The prevailing assumption is that the underlying causes of such diseases, as well as processes that impair memory and cognition, are preliminary changes in the brain’s structure that directly or indirectly affect its function. However, the exact nature of these changes and their mechanisms are not yet fully understood. Accumulating evidence suggests that these changes originate in the supportive cells, particularly microglial cells, which are involved in the central nervous system (CNS) immune system.
A connection has been identified between learning - such as reading, solving puzzles, attending enrichment classes, and more - and the brain’s resistance to neurodegenerative diseases or decline. This has led to the hypothesis that the changes leading to decline may result from reduced nerve cell activity. Findings from cell cultures support this hypothesis.
Based on this understanding, a therapeutic approach called “reminiscence therapy” has been developed in recent years. This method involves exposing elderly individuals to content from their past that is likely to evoke childhood memories, to reactivate old connections between nerve cells. In line with this approach, some elderly care homes are now designed in the style of the 1950s and play their tenants music from their youth to encourage memory retrieval. A 2022 study reviewed the findings of multiple small-scale studies and concluded that elderly individuals exposed to reminiscence therapy treatments experience an improvement in their cognitive and memory functions, report a higher quality of life, and suffer less from depression and other mental disorders.
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