New Brain Cells – Many triggers for Neurogenesis

Before we could observe active changes in the neurons of the brain, neuroscientists assumed the brain was either static, with no new cells, or deteriorating, with cells dying as we age. With increasing technology, scientists can now see that this was wrong.  Important parts of the brain continue to make new cells throughout our lives.

What has been more astounding is that many different events can trigger the production of new neurons, including exercise, psychotherapy, medications, and stimulating environments. This production of new neurons is called neurogenesis. It has also been found that new neurons are associated with increased learning.

A previous post has addressed brain changes including the creation and deletion of new connections through increased budding of dendrites and axons.  These appear to be extremely active and change every day, especially at night when unused connections are actively pruned.  The new connections are related to almost any influence on the brain including words, thoughts, experiences, the environment, meditation, memory, learning and attention.

The creation of new brain cells in adulthood appears to be related to learning and memory, but also plays a significant part in psychiatric illness.

This post will briefly summarize previous posts on increased neuronal connections and then will address newly minted neurons in the brain and how critical they are for learning, as well as mental health.

Recent Research on New Neuronal Connections

Very recent advances in research show an even more active brain than was imagined even several years ago with constant building and eliminating of synapses.  One study, using two photon microscopy, was able to observe glia cells tapping synapses each hour for five minutes in active surveillance.  Those synapses that were not functioning were eliminated. Another imaging study showed microglia brain cells active in building and pruning synapses.  Other studies show that neurons are actively able to alter their neurotransmitters with changing circumstances. Zuo showed that with learning new connections between cells emerged rapidly with dendritic spines often forming spatial clusters near other connections.

New Brain Cells

Ultrasound Picture of Fetal Brain

New brain cells are actively created during fetal development at a fantastic rate, 250,000 new cells per second in the ninth month of pregnancy.  The total number of neurons in  the fetal brain reaches almost a thousand billion (a trillion), which are then pruned to 100 billion in the child, this number, basically, remaining throughout life.  The pruning of cells occurs through experience; those cells not used are eliminated.  In a similar manner connections between these 100 billion cells, up to 10,000 for one neuron, also are created by responding to experience and then pruned if not active

After this fetal period only a relatively small number of cells are made each day and only in very specific places. Neurogenesis occurs definitely in two brain regions, probably in a third region, and perhaps in a fourth.  Because it is very difficult to see live single cells in the human brain and animal research cannot be extrapolated to the human brain, the research into adult human neurogenesis is very difficult.  But, it is proceeding and there is increasing evidence for these four regions.

The first definite region for new cells is the hippocampus, which is critical for learning and memory (specifically, it occurs in the subgranular zone of hippocampus dentate nucleus).  Very recent research has observed new brain cells in a second region.  These new neurons are migrating from an area called the subventricular zone (SVZ) to the forebrain through a path called rostral migratory stream (RMS).

There have been many studies that have shown that new cells also migrate to the olfactory bulb, a region connected with learning of smells.  Older studies have shown that thousands of new inter-neurons reach the olfactory bulb each day.  Clearly memory and new learning of smells were correlated with these new cells.

One recent study didn’t find any new olfactory cells.  A criticism of this study is that the subjects were deceased and had illnesses that would decrease the existence of new brain cells. Also, it has been pointed out that new cells occur for new smell learning.  In a sanitized Western environment there would be few if any new smells and might not trigger new cells.

A very recent finding is the possibility of new cells in the hypothalamus, a very significant region that regulates metabolism. In this study it appeared that fat cells stimulated new neurons to further coordinate metabolism. This could be a very significant finding for research into diet and obesity.

New Learning Means New Cells

One of the most exciting discoveries of the past few years is that new brain cells in the hippocampus are clearly related to learning.  Very significant new research has further clarified that new brain cells are more likely to respond to incoming informationIn contrast older neurons do not respond to the new information but are fixed in working with specific old information responses.  The newer cells are clearly more plastic and show the changes of neuroplasticity.

Also, new neurons were clearly shown to increase the ability to learn and memorize difficult cognitive tasks.

This very exciting recent research by T. Nakashiba shows that the new neurons from neurogenesis in the hippocampus have a distinct function as compared with the older neurons. A form of memory called ‘pattern separation‘ forms distinct new memories based upon specific differences such as remembering by comparing the difference between two different cars.  This requires new neurons. There is also evidence that the newer cells have more widespread connections than the older cells.

Pattern completion‘ is the other form of memory that is based upon detecting specific similarities, such as remembering which car a friend was driving.  This type of memory requires the old neurons.

Depression

By observing the brain, it was found that in depression important areas of the brain sink, even as they have hyperactivity of signaling.  This shrinkage in the brain, with decreased cells and connections, may get worse and worse the longer the depression lasts, making treatment an essential priority.  In other kinds of psychiatric illnesses, such as those where fear is involved, scientists found significantly larger neural regions to trigger anxiety and fear.  The major fear center also grows in children of mothers who have depression.

There are three major ways of helping or curing depression and anxiety.  These methods include certain types of psychotherapies, psychiatric medications, and changes in lifestyle.  All three of these have now been shown to increase the production of new cells in important regions in the brain.

Using imaging devices, scientists can easily see brain changes as a result of psychotherapy. In fact, this involves new cells in addition to increasing connections of existing cells.  Different types of psychotherapies change the brain in different ways, just as different meditation styles change particular regions of the brain. Attention to different tasks, emotions and views change the brain in particular ways.

Medications, when effective in helping depression, have been shown to cause an increase of a very important brain chemical, BDNF brain derived neurotropic factor, which stimulates the creation of new cells.  These molecules are called brain trophic factors, because they help the neurons grow.

New Learning, Exercise

As well as psychotherapy and medications, exercise and so-called “enriched environments” also increase the production of new brain cells in critical regions that help memory and mood.  “Enriched environment” is a research word for being surrounded with increasing caring and increased mental and physical stimulation.  In these enriched environment there is also increased BDNF, increased brain cells and increased learning.

It appears that new learning of any kind involves creation of new brain cells in critical brain regions.  In exercise there appears to be a window of opportunity just after the exercise where the new learning and new brain cells are most robust.  A previous post also emphasized that stage IV sleep also is a time of increased learning in the brain.

Brain Factors that Stimulate or Block New Neurons

There are many other factors that influence BDNF and the production of new neurons.  Lack of appropriate sleep appears to decrease the production of new brain cells through a pathway involving the hormone glucocorticoids. Chronic stress and aging also seem to influence BDNF to decrease new cells.

BDNF

Microbes in the gut also influence hippocampal levels of BDNF.  In gastrointestinal disorders BDNF can be influenced to stimulate depression.  The mechanism of the microbe effect on BDNF and the brain did not occur through the autonomic nervous system, GI neurotransmitters, and inflammation.  It appears to be a direct blood signal to the brain from the microbes.

Another dramatic finding about BDNF involves the HIV virus.  HIV doesn’t infect neurons directly but it dramatically affects them, destroying many neurons and causing dementia.  The mechanism of this dementia has just been discovered.  HIV has a hook on its surface called the gp120 envelope protein, which is used to grab onto blood and glia cells to infect them.  This same hook also grabs onto the precursor to BDNF, called proBDNF.  By grabbing onto this molecule it stops the creation of the active BDNF, which is necessary for new brain cells, and new connections between neurons.  By stopping BDNF it actually kills neurons and causes dementia.

Aging and new cells

The creation of new brain cells is decreased in many aging brains. The two zones in the brain where new cells are definitely arising are very close to numerous blood vessels.  It is, therefore, reasonable to think that stimulation of new cells can occur through blood borne factors.  One blood transmitted factor that influences the creation of new brain cells is called CCL11(CC chemokine ligand 11). A study recently showed that a decrease in the factor called CCL11 was critical for the decrease in new cells in the hippocampus with aging.

Negative Brain Cells

The creation of new cells with new learning and increased memory is generally considered to be very positive.  But, it is important to realize the new learning can be negative as well as positive.  Addiction, for example, is a learned behavior that takes root in the circuits of the brain with new brain cells and new connections which increase with continued use.

A very intriguing study recently showed that when exercise increases brain cells and new learning, this can also prime the brain for addiction.  Just after exercise if cocaine was used, the addiction became much worse because of the neuroplasticity. This is a significant lesson in that we must learn to use our new cells for positive purposes.  Previous posts have shown how meditation and other brain training can increase the ability to focus the mind on positive tasks.

Positive Versus Negative Choice of Brain Cells

The overall message is that there is constant production of new brain cells as we utilize the brain for learning, and especially when engaging in certain self developmental activities such as exercise, psychotherapies, stimulating mental and physical tasks, and certain medications.

Attention to our thoughts, especially including more positive ones, will stimulate new brain cells with increased brain capacity for positive experience.  It appears that the only constant in nature is change, especially in our brains.  And hopefully we will continue to use this change for positive purposes.

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