Neuroplasticity and Neurogenesis

Chapters 2 and 3 of Sharon Begley’s “Train Your MInd, Change Your Brain” cover neuroplasticity and neurogenesis.  Prior to discussing neuroplasticity, how learning takes place needs to be discussed.  To explain how learning takes place psychologist Donald Hebb conceived of cell assemblies.  He proposed that learning and memory were based on the strengthening of synapses.
Somehow either the neuron that fires first in the chain (the presynaptic neuron) or the neuron that fires next (the postsynaptic neuron), or both, change in such a way that the firing of the first is more likely to cause the firing of the second.  Learning and memory involve the firing of large assemblies of these cells.  Hence Hebb’s theory is called cell assembly theory.  Hebb’s maxim is that cells that fire together wire together.

Virtually all the research on neuroplasticity involved animals.  This is because surgery was almost always required. Sensory  or motor connections might be severed, and then observations would be made regarding the effects of these operations.  Sometimes connections were rewired so that animals would see sound or hear light. The late nineteenth psychologist William James had wondered , were scientists were able to alter neuron’s paths so that exciting the ear activates the visual cortex and exciting the eye the auditory cortex, we would be able to  “hear the lightning and see the thunder.”  So James was correct.  And all this research invalidated the longstanding dogma that the nervous system could not be rewired or rewire itself underscoring the reality that the nervous system can and does rewire itself.

The longstanding dogma that new neurons  could not be created, neurogenesis, was more difficult to disprove.   Before cells divide, they make a copy of their DNA.  As cells can’t conjure the double helix out of thin air, biochemicals snag the requisite ingredients from within the cell and assemble them.  One element of DNA, thymidine, lets a radioactive  molecules glom on to it.  When the thymidine becomes incorporated into the brand-new DNA, the DNA has a spot of radioactivity, which can be detected experimentally.  Old DNA does not have this glow.

Joseph Altman, a new neuroscientist at MIT, decided to try the new trick on brains.  By scanning neurons for tell tale glows he figured he would be able to detect newborn DNA, and newborn cells.  He found neurons of adult rats, cats,  and guinea pigs with thymidine—indicating that they had been born after Altman had injected them with the tracer.  He published these finding in three prestigious scientific journals in 1965, 1967, and 1970, yet his claims were ignored,   Altman was denied tenure at MIT and joined the faculty of Purdue University.

Research was done using nonhuman  animals with rich environments.  That is animals who lived in enriched environments with exercise wheels and novel features were compared to animals living in impoverished environments.  The formation and survival  of new neurons increased 15% in a part of the hippocampus called the dentate gyros, which is involved in learning and memory.

To this point humans had not been involved in the research, the reason being that noninvasive brain imaging could not address this issue.  Brains needed to be taken from   dead research participants.  Oncologists injected BrdU into cancer patients because is marks every newborn cell.  This allowed them to assess how many new cancer cells were developing.  The researchers were able to enlist the cooperation of oncologists and their patients.  After these patients succumbed to cancer, their brains could be examined to see if any new  noncancerous cells had been generated.  Thanks to these patients and their oncologists, new neurons, indicating neurogenesis, were found in the hippocampus.

An interesting find was that forced exercise does not promote neurogenesis.  The neuroscientist Gage explained to the Dalai Lama, “Running voluntarily increases neurogenesis and increases learning even in very, very old animals.  It seems like the effects of running on neurogenesis and on learning are dependent on volition.  It has to be a voluntary act.  It is not just the physical activity.

When the neuroscientist Fred Gage sat down with the Dalai Lama it was clear that new neurons arise from neural stem cells in the adult human brain, which persist and support ongoing neurogenesis.  This discovery expanded the possibilities for neuroplasticity.  The neural electrician is not restricted to working with existing wiring, he can run whole new cables through the brain.

In humans new neurons might do more than help with learning.  The hippocampus plays an important role in depression.  In many people suffering from depression, the dentate gyrus oaf the hippocampus  has drastically shrunk.  There is a question of cause and effect, whether another factor caused the hippocampus to shrink leading to depression, or whether depression caused the shrinkage.

New research suggests that people who are suffering from depression are unable to recognize novelty.  Gage said this to the Dalai Lama, “You hear this a lot with depressed people.  Things just look the same.  There is nothing exciting in life.”  “There is also evidence,” Gage said, “that if you can get someone with depression to exercise, his depression lifts.”  So neurogenesis might be the ultimate anti-depressant.  When it is impaired for any reason, the joy of seeing life with new eyes and finding surprises and novelty in the world vanishes.  But when it is restored the world is seen anew.

It is clear that chronic stress impairs neurogenesis, at least in mice.  Gage’s colleague, Peter Ericsson suspects that holds lessons for humans also.  “In lab animals, chronic stress dramatically decreases neurogenesis as well as spatial memory..  When people under stress experience severe memory problems—forgetting their way to work, going into the kitchen and then no remembering why they went in—it is likely that what they’re experiencing is the very negative of stress on the function of the hippocampus due to decreased neurogenesis.”

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