A bombshell of a finding

Gaby

SuperModerator
Moderator
FOTCM Member
This is an article published in Nature Reviews Neuroscience 14, 522 (2013).

The question of whether adult neurogenesis occurs in the human hippocampus has been a hotly debated topic in neuroscience. In a study published in Cell, Frisén and colleagues now settle the debate by providing evidence that around 1,400 dentate gyrus cells are born in the human brain every day.

The authors made use of a birth-dating method that is based on the principle that 14C in the atmosphere is taken up by plants and — because humans eat plants and animals that eat plants — eventually also by humans. As 14C is incorporated into DNA during cell division, the 14C content of a cell is thought to reflect 14C levels in the atmosphere at the time of the birth of the cell. Importantly, atomic bomb testing in the 1950s and 1960s resulted in a spike in atmospheric 14C levels, and levels declined after 1963; this means that the level of 14C in cellular DNA can be used as a relatively precise marker of a cell's birth date.

The authors applied the 14C birth-dating method to whole hippocampi dissected from post-mortem brains donated by individuals who were born in different years in the twentieth century. They separated neurons from non-neuronal hippocampal cells, purified the neuronal DNA and determined 14C levels. Neuronal 14C levels did not match atmospheric 14C levels in the individual's birth year but were either higher (for people born before 1950) or lower (for people born after 1963), suggesting that at least some of the hippocampal cells were born after the year in which an individual was born.

Computer modelling of the data revealed that the best-fit model was one in which 35% of hippocampal cells showed such turnover, whereas the majority did not (that is, they were born during development). Assuming that, in humans, adult neurogenesis would take place in the dentate gyrus rather than in other hippocampal areas (as it does in rodents), and as the dentate gyrus contains about 44% of all hippocampal neurons, this model suggests that about 80% of human dentate gyrus cells undergo renewal in adulthood. This is in striking contrast to the scenario in mice, in which only ~10% of adult dentate gyrus neurons undergo renewal. The study further showed that there is very little decline in the level of hippocampal neurogenesis with ageing in humans, which is again in contrast to rodents.

It is now well established that adult-born neurons have a functional role in the mouse and rat dentate gyrus and olfactory bulb. A previous study using the same neuronal birth-dating method established that no adult neurogenesis takes place in the olfactory bulb and cortex in humans, but the new study has elegantly shown that the situation is different in the dentate gyrus. Whether the adult-born neurons have functional implications in humans remains a topic for future investigation.

Regarding the dentate gyrus:

_http://en.wikipedia.org/wiki/Dentate_gyrus

The dentate gyrus is part of the hippocampal formation. It is thought to contribute to the formation of new episodic memories,[1][2] the spontaneous exploration of novel environments,[2] and other functions...

The molecular layer of dentate gyrus granule neurons receive the hippocampal formation's major excitatory input from the cortex...

The dentate gyrus is thought to contribute to the formation of memories, and to play a role in depression.

Memory

The dentate gyrus is one of the few regions of the adult brain where neurogenesis (i.e., the birth of new neurons) takes place. Neurogenesis is thought to play a role in the formation of new memories. New memories could preferentially use newly formed dentate gyrus cells, providing a potential mechanism for distinguishing multiple instances of similar events or multiple visits to the same location.[20] A Study at the Human Nutrition Research Center on Aging showed that feeding blueberry extract to older rats for a short time frame increases neurogenesis in the dentate gyrus. This increased neurogenesis is associated with improved spatial memory, as seen through performance in a maze.[21]

Stress and depression

The dentate gyrus may also have a functional role in stress and depression. For instance, neurogenesis has been found to increase in response to chronic treatment with antidepressants.[22] On the contrary, however, the physiological effects of stress, often characterized by release of glucocorticoids such as cortisol, as well as activation of the sympathetic division of the autonomic nervous system, have been shown to inhibit the process of neurogenesis in primates.[23] Both endogenous and exogenous glucocorticoids are known to cause psychosis and depression,[24] implying that neurogenesis in the dentate gyrus may play an important role in modulating symptoms of stress and depression.[25]

Other

Some evidence suggests neurogenesis in the dentate gyrus increases in response to aerobic exercise.[26] Several experiments have shown neurogenesis (the development of nerve tissues) often increases in the dentate gyrus of adult rodents when they are exposed to an enriched environment.[27][28] The dentate gyrus is also known to serve as a pre-processing unit. When information enters, it is known to separate very similar information into distinct and unique details. This prepares the relevant data for storage in the hippocampal CA3 section.[29]
Spatial behavior

Studies have shown that after destroying about 90% of their dentate gyrus (dg) cells, rats had extreme difficulty in maneuvering through a maze they had been through prior to the lesion being made. When being tested a number of times to see whether they could learn a maze, the results showed that the rats did not improve at all, indicating that their working memories were severely impaired. Rats had trouble with place strategies because they could not consolidate what they had learned about a maze they had just run into their working memory and could not remember it when maneuvering through the same maze in a later trial. Every time a rat entered the maze, the rat behaved as if it was seeing the maze for the first time.[30]

Blood sugar

Studies by researchers at Columbia University Medical Center indicate poor glucose control can lead to deleterious effects on the dentate gyrus.[31]
 
Interesting I could use this info the learn more about the process of controlling stress.. along with the info from Eiriu Eolas.. and once again is important to keep the sugar in a minimum state in our body!
 
More on dentate gyrus: it seems that d.g. not only contributes to depression and/or anxiety but also plays a key role in learning (the formation of new memories must be a part of the function), and there are different parts of it responsible for anxiety and for learning. I'm not very excited about the deep-brain stimulation possibility in treating PTSD and other anxiety/depression disorders though...

http://www.news-medical.net/news/20130307/Selective-activation-of-the-dentate-gyrus-can-reduce-anxiety-without-affecting-learning.aspx

Published on March 7, 2013

Selective activation of the dentate gyrus can reduce anxiety without affecting learning

Columbia University Medical Center (CUMC) researchers have found the first evidence that selective activation of the dentate gyrus, a portion of the hippocampus, can reduce anxiety without affecting learning. The findings suggest that therapies that target this brain region could be used to treat certain anxiety disorders, such as panic disorder and post-traumatic stress syndrome (PTSD), with minimal cognitive side effects. The study, conducted in mice, was published today in the online edition of the journal Neuron.

The dentate gyrus is known to play a key role in learning. Some evidence suggests that the structure also contributes to anxiety. "But until now no one has been able to figure out how the hippocampus could be involved in both processes," said senior author Rene Hen, PhD, professor of neuroscience and pharmacology (in psychiatry) at CUMC.

"It turns out that different parts of the dentate gyrus have somewhat different functions, with the dorsal portion largely dedicated to learning and the ventral portion dedicated to anxiety," said lead author Mazen A. Kheirbek, PhD, a postdoctoral fellow in neuroscience at CUMC.

To examine the role of the dentate gyrus in learning and anxiety, the investigators used a state-of-the-art technique called optogenetics, in which light-sensitive proteins, or opsins, are genetically inserted into neurons in the brains of mice. Neurons with these genes can then be selectively activated or silenced through the application of light (via a fiber-optic strand), allowing researchers to study the function of the cells in real time. Previously, the only way to study the dentate gyrus was to silence portions of it using such long-term manipulations as drugs or lesions, techniques that yielded conflicting results.

In the current study, opsins were inserted into dentate gyrus granule cells (the principal cells of the dentate gyrus). The researchers then activated or silenced the ventral or dorsal portions of the dentate gyrus for three minutes at a time, while the mice were subjected to two well-validated anxiety tests (the elevated plus maze and the open field test).

"Our main findings were that elevating cell activity in the dorsal dentate gyrus increased the animals' desire to explore their environment. But this also disrupted their ability to learn. Elevating activity in the ventral dentate gyrus lowered their anxiety, but had no effect on learning," said Dr. Kheirbek. The effects were completely reversible - that is, when the stimulation was turned off, the animals returned to their previous anxiety levels.

"The therapeutic implication is that it may be possible to relieve anxiety in people with anxiety disorders by targeting the ventral dentate gyrus, perhaps with medications or deep-brain stimulation, without affecting learning," said Dr. Hen, who is also director of the Division of Integrative Neuroscience, The New York State Psychiatric Institute, and a member of The Kavli Institute for Brain Science. "Given the immediate behavioral impact of such manipulations, these strategies are likely to work faster than current treatments, such as serotonin reuptake inhibitors."

According to Dr. Hen, such an intervention would probably work best in people with panic disorder or PTSD. "There is evidence that people with these anxiety disorders tend to have a problem with pattern separation - the ability to distinguish between similar experiences," he said. "In other words, they overgeneralize, perceiving minor threats to be the same as major ones, leading to a heightened state of anxiety. Such patients could conceivably benefit from therapies that fine-tune hippocampal activity."

Dr. Hen and his team are currently exploring strategies aimed at modulating the activity of the ventral dentate gyrus by stimulating neurogenesis in the ventral dentate gyrus. "Indeed the dentate gyrus is one of the few areas in the adult brain where neurons are continuously produced, a phenomenon termed adult hippocampal neurogenesis," added Dr. Hen.
 
Back
Top Bottom