The Brain map of a monkey’s left hand.

Situation 1: Overstimulation

After the third and second digit of this monkey are overstimulated the corresponding brain maps increase in size.

Situation 2: Amputation

This monkey’s third digit has been amputated and no longerreceives stimulation. Due to this the corresponding brainmap has been eliminated and the extra space is now used bydigit two and four for processing.

Jordan Dixon, Maxime Goovaerts

WRA 110: Section 741

-2011-

The Past, Present, and Future of Neuroplasticity

By

Jordan Dixon

Maxime Goovaerts

WRA 110, Sec. 741

Michigan State University

April 18, 2011

Word Count: 2,450

Neuroplasticity 1

The Past, Present, and Future of Neuroplasticity

Did you know that before birth your brain eliminates around half of its neurons?

(Brain Facts par.1) This concept is called exuberance followed by regression. (Nunez

Lecture Notes) At first your brain will develop too many neurons and then prune those

that are not being used during its organizational period. The brain’s organizational

period begins right before birth and continues into adulthood. During the brain’s

organizational period the structure of the brain is going through serious changes and

has naturally higher levels of plasticity. (Nunez Lecture Notes)

Neuroplasticity, as defined by Medicine Net, is “the brain’s ability to reorganize

itself by forming new neural connections throughout life.” (“Definition of Neuroplasticity”

par.1) The theory of neuroplasticity states that thinking, learning, and acting change the

brain’s physical structure and functional organization. When plasticity was first

discussed in the early 1900’s, researchers believed that the lower brain was

unchangeable after it developed. They also believed that the frontal lobe and other parts

of the brain that were involved in the memory forming process were very plastic. The

neuron doctrine came out in the 1920s and showed the steps of development in

knowledge about plasticity from all the experiments done by researchers. From 1949-

1950 there was a breakthrough in the field of neuroplasticity. Donald Hebb discovered

that memories were stored throughout the brain in networks of neurons, also known as

assemblies. Later neuroscientists discovered something now known as the ‘critical

period’ where neurons are greatly affected by experience and are most impacted by

change.

Neuroplasticity 2

It was not until recently that neuroscientists discovered what chemicals were

responsible for plasticity. While running trials on mice, measuring the levels of

neurotransmitters found during development exceptionally high levels of acetylcholine

were found during the sensitive period in the brains developmental stage. Through

further research, scientists discovered that Lynx1 was the molecule responsible for

braking neuroplasticity as the brain aged. The region of the brain that develops

acetylcholine is called the nucleus basalis. The nucleus basalis can be activated when

electronically stimulated. Antidepressants increase the level of brain plasticity in the

user. However antidepressants are not drugs that someone without depression could

take to increase their plasticity. This is because antidepressants simply stop the rigid

state of mind that depression creates. Neuroplasticity is a fascinating field of science

that is constantly changing.

Several decades ago, many believed that the lower brain and neocortical areas

of the brain remained unchangeable after they were developed. It was believed that

areas of the brain related to memory formation such as the hippocampus and dentate

gyrus are highly plastic and new neurons continue to be produced through adulthood.

However, after decades of research it is now known that there are changes even in the

lowest neocortical processing areas. These changes can have a great impact on the

pattern of neuronal activation in response to experience.

Plasticity was first proposed by Santiago Ramón y Cajal. It was him who first

thought of the neuron doctrine even though this idea was not accepted for another fifty

years. (Shepherd) The neuron doctrine states that the nervous system is made up of

individual cells. (Shepherd 134) Ramon y Cajal did not come up with the neuron

Neuroplasticity 3

doctrine on his own but rather created it by compiling work done by other researchers.

The neuron doctrine contains several low level theories and was put together into higher

level theories that explain the main data that is in the lower level theories. (Shepherd

135)

Then Karl Lashley started to experiment on rats. (Orbach 23) Lashley trained the

laboratory rats to perform certain tasks, after Lashley was sure the rats had developed

these skills he then tampered certain parts of the rats cortex. (Orbach 33) When

Lashley did this to the rats, it had a big impact in the memory areas of the brain. This

then led Lashley to experiment on cerebral localization, for which he became very

famous for. (Orbach 34) Cerebral localization was the field in psychology that had the

most controversies in the earlier years of the 1900’s. Through experiments Lashley held

on his rats, Lashley hypothesized that there was an area in the brain where memories

of previously learned responses were stored called the engram. (Orbach 43) So Lashley

set up various mazes to have the rats to attempt to find their way through to the exits.

(Orbach 43) Lashley made the various mazes with different sizes and difficulties.

(Orbach 43) After the rats had memorized their way through the maze to the exits,

Lashley performed different lesions on the rat’s brains, thinking that he would find a way

to remove the engrams the rat’s brains created. (Orbach 44) Unfortunately, after

multiple years of research on these rats, Lashley was unable to find these so called

“engrams”. (Orbach 46)

Canadian psychologist Donald Hebb hypothesized in 1949 that memories were

stored in the brain in networks of neurons that Hebb called cell assemblies. (Hebb 182)

He thought that through learning experiences the networks of neurons come to

Neuroplasticity 4

represent specific objects or concepts. Hebb then hypothesized that when presynaptic

and postsynaptic neurons shoot action potentials together, the power of the synaptic

connections between the presynaptic and postsynaptic neurons are improved. (Hebb

182) Therefore, the cells that fire together would then wire together. Then in 1950,

Donald Hebb took laboratory rats home to treat like pets and realized that the rats

showed much greater performance than the rats that were raised in the laboratory.

(Hebb 183)

During the critical period the effects of experience have the most significant

impact on the brain’s neurons. (Hubel 422) This is also known as plasticity. For

example, if an infant fails to experience normal visual stimulation in one of their retina’s

and is not fixed early in development, the developmental failure and resulting shortage

cannot be prevented. But if the infant’s eyes are aligned early in the developmental

stage, the developmental and resulting shortage can be prevented.

In the past, scientists believed that this critical period only existed in children.

Only recently did neuroscientists begin discovering various cases where plasticity

played a role in adults. Mark Rosenzweig is an American research psychologist who

focused on animal studies concerning neuroplasticity. He led trials with rats to discover

what was happening in the brain that allowed brains to reorganize so easily.

Rosenzweig raised a group of rats in enriched environments and another group in

impoverished environments. (Doidge 43) He found that the rats in enriched

environments learn better than those placed in more impoverished locations. Rosenzeig

linked this to the level of acetylcholine found in these rats, the more adept the rats were

Neuroplasticity 5

at learning tasks the higher levels of acetylcholine were found produced by their brains.

(Doidge 43)

This correlation between plasticity and the neurotransmitter acetylcholine was

confirmed by Hensch and his group of scientists. Hensch and his fellow researchers

started by identifying how venom from a banded krait works and discovered that it

functioned similarly to a molecule naturally produced in brains, Lynx1. Lynx1 serves as

a kind of brake in the brain that suppresses the tendency of neurons to grow. (Castro

par.2) Hensch and his group measured the levels of Lynx1 in the brains of mice and

found that the concentrations stayed low during the known critical period but increased

steadily after that; it followed the trend of neuroplasticity. In order to confirm their belief

Hensch took this one step further by genetically removing Lynx1 from the mice’s brains

They found that even after the previously discovered period of high plasticity the mice

could still perform serious organizational changes to their brain maps. In this experiment

the mice were able to drastically change their brain map, even past the critical period.

Hensch sutured one of the mice’s eyes shut and recorded the changes happening in the

visual cortex. What Hensch discovered was that, unlike the control mice, mice without

Lynx1 could still undergo ocular dominance shifts well into adulthood. Hensch and his

colleagues discovered that Lynx1 works by blocking receptors for the neurotransmitter

acetylcholine. (par.13 Castro)

This new research suggests that plasticity can be enhanced by delivering drugs

that boost levels of acetylcholine. (par.15-16 Castro) While this may sound like a great

idea it is something that we should tread carefully around. Increasing plasticity may

cause current knowledge and memories to be lost more easily. This would happen

Neuroplasticity 6

because plasticity facilitates changes in brains, such as reorganization and even

deletion of knowledge and memories. This is why brains normally decrease in plasticity

as they age. (par.15-16 Castro)

The Nucleus Basalis is a region of the brain with high concentrations of

acetylcholine that when stimulated. It facilitates the ability to learn in the brain. Michael

Merzenich, professor/neuroscientists at the University of California, and his colleague,

Michael Kilgard, set up an experiment on adult rats where they artificially turned on the

nucleus basalis. Their purpose was to see the effects that this had on the rat’s

neuroplasticity; whether the rats would learn without a reward. They artificially turned on

the nucleus basalis by inserting microelectrodes and using an electrical current to keep

the nucleus basalis turned on. They then exposed the rats to a certain sound frequency

(9 Hz) to see if the rats would develop a brain map location for this frequency, the way

other animals do it during their critical period. After a week of exposing these rats to the

frequency with their nucleus basalis turned on their brain maps had massively changed;

expanding the already existent 9 Hz brain map. Merzenich and Kilgard had discovered

an artificial way to reopen the critical period in adults. (Doidge 83)

Antidepressants are known to increase plasticity in users; this however is a

deceiving statement. The reason why antidepressants increase plasticity is because

they address the symptoms associated with depression. (Andrade and Rao 378) One of

these symptoms is lack of plasticity. Depression is not caused by a chemical in balance

in the brain, but rather a “hardwiring of the brain.” (Andrade and Rao 379) It is this solid

state of mind that keeps the individual from being open to new ideas and what makes it

so hard to recover. Stress is another important symptom of depression, the reason why

Neuroplasticity 7

this symptom is so important is because stress is very physically tolling on the brain. So

stress and depression are what causes the low in plasticity mental state. (Andrade and

Rao 379)

Neuroplasticity has quite the past, but will have an even larger future. As stated

by Dr. Hammond, a professor from Stanford University, “New research aims to develop

lifestyle behaviors and medications that could improve normal brain development as

well as repair damaged brains.” (Hammond par. 17) There is research being conducted

for treatment of HD and Parkinson’s by cell transplantation and/or physical therapy.

Transcranial Magnetic Stimulation (TMS), as defined by Mayo Clinic, is a procedure that

uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of

depression. (“Transcranial Magnetic Stimulation” par.1) TMS is used to help guide the

process of brain reorganization, but is not ready for clinical use until it is determined

how effective it is, which treatments are best, and if there are any long-term side effects.

Being able to increase brain reorganization, or plasticity, could bring about faster and

more successful recoveries from damage to the brain. (Hammond par. 18)

Drugs are another future of neuroplasticity; Dr. Hensch’s group used infusions of

drugs that raised levels of acetylcholine in the mice’s brains. (Castro Par.14) However

the future of drugs which will affect neuroplasticity is not yet clear because there has not

been any research done on humans, and not enough done on animals. On top of the

lack of research there is an ethical issue concerning this; is changing the plasticity of

one’s brain ‘ethically right’ when it comes to learning new skills? According to Castro

drugs effecting plasticity will most likely be used to stop senescence and cognitive

Neuroplasticity 8

decline that comes naturally with age. (Castro par.16) Neuroplasticity is a constantly

developing field of science and since it’s relatively new there’s still too much to learn.

Conclusion

Neuroplasticity started being researched in the early 1900’s where even then the

idea of plasticity was not accepted by most researchers. Then when we reached the

1950’s experiments done by Donald Hebb provided enough evidence to prove that we

have memories stored in networks of neurons. In the 2000s new neuroscientists began

taking over the field of plasticity. Mark Rosenzweig first discovered that plasticity was

effected by acetylcholine. Hensch confirmed this by finding a correlation between

Lynx1, a molecule that increased in density in the brains of mice as their brains naturally

became less plastic, and the chemical acetylcholine. Through trails with mice, Hensch

discovered that by removing the genetic code that the mice used to create Lynx1 he

could effectively stop their brains natural decline. Without the Lynx1 there was nothing

to decrease the concentration of acetylcholine. But directly changing the chemicals in

the brain was not the only way to recreate the critical period of brain development.

Michael Merzenich, a professor at the University of California, found that the by

electrically stimulating the nucleus basalis he could drastically increase the ability of

mice to change their brain maps. After a week of exposing them to a frequency of 9 Hz

their brain maps for that frequency had greatly increased. Antidepressants also affect

brain plasticity but they should not be confused as a drug that nondepressed individuals

should take. As explained in the Journal of Psychology by Chittaranjan Andrade and N.

Sanjay Kumar Rao antidepressants fix the symptoms of depression, one of which is

Neuroplasticity 9

lack of plasticity. Depressed adults are stuck in a single state of mind and it’s

antidepressants that allow them to move on.

The great amount of research concerning neuroplasticity is naturally leading

towards a medical possibilities: procedures and drugs. TMS is a procedure to help with

recovering damaged areas of the brain and help the process of brain reorganization.

Researchers are experimenting to try to find cures to syndromes like HD and

Parkinson’s through treatments similar to TMS. Drugs that will change levels of

plasticity will most likely be used to stop senescence but do have potential to be

abused. Changes in the idea of neuroplasticity have been quite drastic in the past

hundred years. Plasticity, which was first proposed by Santiago Ramón y Cajal, started

off as an idea which was not fully accepted for another fifty years and now, as scientists

are working diligently to perfect a method of increasing plasticity the possible uses of

technology are being discussed. Will this be the end of brain disorders? With the ability

to control plasticity it seems that this is becoming one very real possibility.

Neuroplasticity 10

Works Cited

"Brain Facts." Posit Science. Web. 12 April 2011. <http://www.positscience.com>.

Chittaranjan Andrade and N. Sanjay Kumar Rao. "How Antidepressant Drugs Act: APrimer on Neuroplasticity as the Eventual Mediator of Antidepressant Efficacy."Indian Journal of Psychiatry 52.4 (2010): 378. ProQuest Research Library. Web.21 Mar. 2011.<http://www.proquest.msu.edu>

Castro, Jason. "Understanding the Brain's "Brake Pedal" in Neural Plasticity." ScientificAmerican(2011): n. pag. Web. 20 Mar 2011.<http://www.scientificamerican.com>.

Doidge, Norman. The Brain that Changes Itself: Stories of Personal Triumph from theFrontiers of Brain Science. Penguin Group USA, 2007. Print. 12 April 2011.

Hammond, K. “Neuroplasticity.” The Brain’s Natural Reparatory Ability. HOPES, 22 Aug2002. Web. 7 Apr 2011. <http://hopes.stanford.edu>.

Hebb, Donald (1949). The Organization of Behavior. John Wiley & Sons Inc. Learning-induced multiple synapse formation in rat cerebellar cortex. Neurosci Lett. 2002Nov 8;332(3):180-184. Print. 12 April 2011.

Hubel DH, Wiesel TN: The Period of Susceptibility to the Physiological Effects ofUnilateral Eye Closure in Kittens. J Physiol. 1970 Feb;206(2):419-436. Print. 12April 2011.

Kopeloff N, Kennard MA, Pacella BL, Kopelhoff LM, Chusid JG.: Section of corpuscallosum in experimental epilepsy in the monkey. Arch Neurol Psychiatry. 1950May;63(5):719-27. Print. 12 April 2011.

"Neuroplasticity." Med Terms 2004. Medicine Net. Web. 20 Mar 2011<http://www.medterms.com>.

Nunez, Joseph. Lecture Notes. PSY 209 - Brain and Behavior. Spring 2011. MichiganState University. East Lansing, Michigan.

Shepherd, Gordon M. Foundations of the Neuron Doctrine. New York: Oxford UniversityPress, 1991. Print. 12 April 2011.

“Transcranial Magnetic Stimulation.” 22 Jul 2010. Mayo Clinic. Web. 20 Mar 2011<http://mayoclinic.com>.

Neuroplasticity 11

Works Cited – GraphicsNunez, Joseph. Power Point (DATE). PSY 209 - Brain and Behavior. Spring 2011.

Michigan State University. East Lansing, Michigan.