When the human body first experiences stress adrenaline takes over & causes a chain-reaction within the nervous system.
1. The heart begins to beat faster....
2. The sizes of the body’s blood vessels are changed.....
3. The body actually prepares itself for a frightening or emotional event....
Even though the humans that are in existence today aren’t in constant physical danger from wild predators
as our pre-historic ancestors were, we still experience this familiar fight-or-flight reaction due to a great deal of different
types of stressors.
There are 2 main types of stress experienced by humans:
chronic
emergency-induced
The chronic type of stress can be particularly harmful to the brain because of hormones & chemicals referred to as glucocorticoids or GC’s.
When the body experiences a rush of adrenaline which is accompanied by stress, a portion of our brain called the adrenal cortex begins to release these GC’s which are useful for dealing with the
emergency-type of stressors.
Chemicals such as cortisol, hydrocortisone & corticosterone
act together to increase the production of glucose, constrict blood vessels & essentially help our brains deal with or
regulate stress.
The GC’s tell our brain either to calm down or to boost its levels of awareness & reaction in order to deal with the issue at hand. These glucocorticoids also affect memory
functioning, especially in the hippocampus region of the brain.
While the GC’s may help us remember frightening or stressful events so that we are better able to deal with them in the future, they can also be harmful to the delicate neurons of the brain.
Prolonged periods of stress or depression may actually lead to the damage or even the death of certain neurons, especially those within the memory center of the brain.
It’s important to remember that different people react differently to stressors; one person
may be able to move on from a trying event while another may suffer from serious psychological effects from a similar event
or situation.
Learning if your stress is chronic or acute is critical for counteracting the negative affects it has on the brain. Those people who are prone to anger, anxiety, depression & who suffer from low self-esteem are far more likely to experience damage to the brain than their calmer, more relaxed peers.
Most every one of us experiences bouts of depression or periods of “the blues” at some point in our lives, but a person who is constantly angry or depressed may require medical or professional assistance.
While it may be possible to recover from depression thru various means such as drug therapy or counseling, the long-term affects on the brain are still largely unknown.
Doctors have recently reported that as many as 50% of patients who experienced
periods of major depression also possessed high levels of cortisol, which as we know can have negative effects on the brain & it’s cells.
A recent study conducted by The Washington University School of Medicine located in St. Louis,
Missouri has shown conclusive evidence of damage to the brain’s neurons in people suffering from depression.
Even those people who had been depressed years prior to the testing still showed signs of brain damage, as much as 12-15% cell atrophy in their hippocampus, resulting
in the loss of an infinite number of memory cells.
Aerobic exercise is
an excellent way to reduce stress & its negative effects on the brain. By engaging in some sort of physical activity the body is able to relax, relieve levels of tension & stress & burn off nervous energy all at the same time.
Endorphins, which are the “feel good” chemicals produced within the brain, are dramatically increased
when we exercise which in turn makes both the body & the mind feel better.
Not surprisingly, self-esteem can also even be lifted with regular exercise as well as an increased overall body image.
In his book “Saving Your Brain” Dr. Jeff Victoroff theorizes that the cultural evolution
& fast-pace of today’s society has essentially overwhelmed the capabilities of the brain.
However, by simply relaxing, slowing ourselves down & learning how to better deal with the common stressors of every day life we can literally save
ourselves from brain damage.
Introduction: The 3 Units of the Human Brain Júlio Rocha do Amaral, MD & Jorge Martins de Oliveira, MD, PhD
Throughout its evolution,
the human brain has acquired 3 components that progressively appeared & became superimposed, just like in an archeological
site:
the oldest: located underneath & to the back
the next one: resting on an intermediate position
the most recent: situated on top & to the front.
They are, respectively:
1. The archipallium or primitive (reptilian) brain, comprising the
structures of the brain stem - medulla, pons, cerebellum, mesencephalon, the oldest basal nuclei - the globus pallidus &
the olfactory bulbs.
It corresponds to the reptile
brain, also called "R-complex," by the famous neuroscientist Paul MacLean.
2. The paleopallium or intermediate (old mammalian) brain, comprising
the structures of the limbic system. It corresponds to the brain of the inferior mammals.
3.The neopallium, also known as the superior or rational (new mammalian)
brain, comprises almost the whole of the hemispheres (made up of a more recent type of
cortex, called neocortex) & some subcortical neuronal groups.
It corresponds to the brain
of the superior mammals, thus including the primates & consequently, the human species.
These 3 cerebral layers appeared,
one after the other, during the development of the embryo & the fetus (ontogenesis),
recapitulating, chronologically, the evolution of animal species (phylogenesis),
from the lizards up to the homo sapiens.
According to Maclean, they're
3 biological computers which, although interconnected, retained, each one, "their peculiar types of intelligence, subjectivity,
sense of:
time & space
memory
mobility
other less specific functions."
Actually, we have 3 cerebral
units in a single brain. The primitive one is responsible for self preservation. It's there that the mechanisms of aggression
& repetitive behavior are developed.
It's there that occur the instinctive
reactions of the so-called reflex arcs & the commands which allow some involuntary actions & the control of
certain visceral functions (cardiac, pulmonary, intestinal, etc), indispensable
to the preservation of life.
The development of the olfactory
bulbs & their connections made possible an accurate analysis of olfactory stimuli & the improvement of answers
oriented by odors, such as approach, attack, flight & mating.
Throughout evolution, some
of these reptilian functions were lost or minimized (in humans, the amygdala & the
entorhinal cortex are the only limbic structures that connect with the olfactory system).
It's also in the R-complex
that started the first manifestations of the phenomena of ritualism, by means of which the animal tries to define its hierarchic
position inside the group & to establish its own space in the ecological niche
In 1878, the French neurologist
Paul Broca called attention to the fact that, on the medial surface of the mammalian brain, right underneath the cortex, there
exits an area containing several nuclei of gray matter (neurons) which
he denominated limbic lobe (from the Latin word "limbus" that implies the idea of circle, ring, surrounding, etc) since it
forms a kind of border around the brain stem (in another part of this text we shall write
more about these nuclei).
The entirety of
these structures, that, years later would receive the name of "limbic system", developed with the emergence of the
inferior (primitive) mammals.
This system commands
certain behaviors that are necessary for the survival of all mammals. It gives rise & modulates specific functions
that allow the animal to distinguish between the agreeable & the disagreeable.
Here specific affective
functions are developed, such as the one that induces the females to nurse & protect their toddlers, or the one
which induces these animals to develop ludic behaviors (playful moods).
Emotions &
feelings, like wrath, fright, passion, love, hate, joy & sadness, are mammalian inventions, originated in the limbic
system. This system is also responsible for some aspects of personal identity & for important functions related to memory.
And, when
the superior mammals arrived on the Earth, the third cerebral unit was finally developed : the neopallium or rational brain,
a highly complex net of neural cells capable of producing a symbolic language, thus enabling man to exercise skillful intellectual
tasks such as reading, writing & performing mathematical calculations.
The neopallium
is the great generator of ideas or, as expressed by Paul MacLean, "it is the mother of invention and the father of abstractive
thought".
The Reptilian Brain.
The archipallium or primitive (reptilian) brain, or "Basal Brian" - (the
green section of the above picture of the brain), called by MacLean the "R-complex", includes the brain stem and the
cerebellum, is the oldest brain.
It consists of the structures
of the brain stem - medulla, pons, cerebellum, mesencephalon, the oldest basal nuclei - the globus pallidus and the
olfactory bulbs. In animals such as reptiles, the brain stem and cerebellum dominate. For this reason it is commonly
referred to as the "reptilian brain."
It has the same type
of archaic behavioral programs as snakes and lizards. It is rigid, obsessive, compulsive, ritualistic and
paranoid, it is "filled with ancestral memories." It keeps repeating the same behaviors over and over again, never learning
from past mistakes (corresponding to what Sri Aurobindo calls the mechanical Mind).
This brain controls muscles,
balance and autonomic functions, such as breathing and heartbeat. This part of the brain is active, even in deep sleep.
The Limbic System
(Paleomammalian brain). - (the red section of the above picture of the brain)
In 1952 MacLean first
coined the name "limbic system" for the middle part of the brain. It can also be termed the paleopallium or intermediate
(old mammalian) brain. It corresponds to the brain of the most mammals,
and especially the earlier ones.
The old mammalian brain
residing in the limbic system is concerned with emotions and instincts, feeding, fighting, fleeing, and sexual behaviour. As MacLean observes, everything in this emotional
system is either "agreeable or disagreeable". Survival depends on avoidance of pain and repetition of pleasure.
When this part of the brain is stimulated
with a mild electrical current various emotions:
fear
joy
rage
pleasure
pain, etc
are produced. No emotion has been found to reside in one place for very long. But the Limbic system as a whole appears to be the primary seat
of emotion, attention, and affective (emotion-charged) memories.
Physiologically, it includes
the the hypothalamus, hippocampus, and amygdala. It helps determine valence (e.g.,
whether you feel positive or negative toward something, in Buddhism referred to as vedena - "feeling")
and salience (e.g., what gets your attention); unpredictability, and creative
behavior.
It has vast interconnections
with the neocortex, so that brain functions are not either purely limbic or purely cortical but a mixture of both.
MacLean claims to have found
in the Limbic system a physical basis for the dogmatic and paranoid tendency, the biological basis for the tendency
of thinking to be subordinate feeling, to rationalize desires. He sees a great danger in all this limbic system power.
As he understands it, this
lowly mammalian brain of the limbic system tends to be the seat of our value judgements, instead of the more advanced neocortex.
It decides whether our higher brain has a "good" idea or not, whether it feels true and right.
The Neocortex, cerebrum, the
cortex , (the blue section of the picture of the brain above) or an alternative term, neopallium,
also known as the superior or rational (neomammalian) brain, comprises
almost the whole of the hemispheres (made up of a more recent type of cortex, called neocortex)
and some subcortical neuronal groups.
It corresponds to the brain
of the primate mammals and, consequently, the human species. The higher cognitive functions which distinguish Man from
the animals are in the cortex. MacLean refers to the cortex as "the mother of invention and father of abstract
thought."
In Man the neocortex takes
up two thirds of the total brain mass. Although all animals also have a neocortex, it is relatively small, with few
or no folds (indicating surface area and complexity and development).
A mouse without a cortex can act in fairly normal way (at least to superficial appearance),
whereas a human without a cortex is a vegetable.
The cortex is divided into
left and right hemispheres, the famous left and right brain. The left half of the cortex controls the right side of
the body and the right side of the brain the left side of the body. Also, the right brain is more spatial, abstract,
musical and artistic, while the left brain more linear, rational, and verbal.
The neurologist Paul MacLean
has proposed that our skull holds not one brain, but three, each representing a distinct evolutionary stratum that has formed
upon the older layer before it, like an archaeological site:
He calls it the "triune brain."
MacLean, now the director
of the Laboratory of Brain Evolution and Behavior in Poolesville, Maryland, says that three brains operate like "three interconnected
biological computers, [each] with its own special intelligence, its own subjectivity, its own sense of time and space and
its own memory."
He refers to these three brains
as the neocortex or neo-mammalian brain, the limbic or paleo-mammalian system, and the reptilian brain, the brainstem and
cerebellum (see above diagram).
Each of the three brains is connected
by nerves to the other two, but each seems to operate as its own brain system with distinct capacities.
This hypothesis has become
a very influential paradigm, which has forced a rethink of how the brain functions. It had previously been assumed that the
highest level of the brain, the neocortex, dominates the other, lower levels. MacLean has shown that this is not the case,
and that the physically lower limbic system, which rules emotions, can hijack the higher mental functions when it needs to.
It is interesting that many
esoteric spiritual traditions taught the same idea of three planes of consciousness and even three different brains. Gurdjieff
for example referred to Man as a "three-brained being."
There was one brain for the spirit,
one for the soul, and one for the body. Similar ideas can be found in Kabbalah, in Platonism, and elsewhere, with the
association spirit - head (the actual brain), soul - heart, and body in
the belly.
Here we enter also upon the
chakra paradigm - the idea that points along the body or the spine correspond to nodes of consciousness, related in an ascending
manner, from gross to subtle.
How Marriage Helps Your Brain
Does matrimony make you smarter? The latest science says: I do
Thomas Crook, PhD, Prevention
I dedicated a recent book,
The Memory Advantage, to my wife, Kay, writing: "I knew when I met her that she would be unforgettable." One of the
reasons Kay made such an impact on me is that she is devoted to the pursuit of knowledge — about everything from movie
blockbusters and interior design to 18th-century epic poetry and primitive art.
Each day, Kay makes a point
of learning new information and passing much of it on to me in the evening. For example, she recently read a book called
The Intellectual Devotional (published by Rodale, which also publishes Prevention),
from which we both learned the origin of John Milton's epic poem "Paradise Lost," the history of the Lascaux cave paintings
in France, and more. I, too, share with Kay much of what I learn every day, and after years of doing this, we've become each
other's best teacher.
From my perspective as a neuroscientist,
this is ironic because the changes that occur in the brain during the early stages of love are not conducive to intellectual pursuits. The feeling of euphoria, the sometimes obsessive desire to be with your beloved... all make concentration on anything else almost impossible.
Using functional magnetic resonance
imaging, researchers have actually observed the effects of love on the brain. When people in the early stages of infatuation
are shown photos of their sweethearts and told to think about them, areas of the brain rich in the chemical dopamine are activated. Dopamine produces very powerful pleasurable sensations. Cocaine and amphetamine, for example, produce their
effects by spurring the release of dopamine.
As relationships mature, however,
those areas are less responsive to the mere sight of one's lover. To be successful, the relationship must evolve from dopamine-driven euphoria to a more mindful cultivation of love and respect. Flowers and
candlelight dinners help, but so do exploring and experiencing the world together. In fact, one area of the brain that "lights
up" in these later stages of love is the cortex, the same place where information is stored and rational decisions are made.
As I've stressed in previous
columns, new information builds fresh neural networks at any age. Here are some ways to strengthen your marriage (and get smarter in the process):
Research shows that men and
women use different areas of the brain when viewing films, resulting in different perspectives and insights.
Throw a party for a diverse group and then debrief each other
the next day
Areas of the brain involved
in learning and memory can be stimulated by social interaction, and you may be surprised at how differently the two of you
interpret the evening's party politics.
Learn a language together
Gradually incorporate new words
and phrases into your conversations. Or sign up for Merriam-Webster's "Word of the Day." It's a free service (m-w.com) that delivers the definition and origin of a new word via e-mail
each day.
Take on a home project to learn each other's skills
There is no reason a wife
can't rewire a lamp or, speaking from experience, a husband can't learn about wall colors other than white. At the very least,
learning new skills together gives you and your spouse something to talk about other than the kids and work
Get some game!
Try to outsmart your spouse at one of our all-new fun and challenging
games at prevention.com/braingames.
Thomas Crook, PhD, a clinical psychologist, has conducted extensive
research to improve our understanding of how the brain works. He is a former research program director at the National Institute
of Mental Health and is CEO of Cognitive Research Corp. in St. Petersburg, FL.
How Stress Symptoms Affect Brain Function By
Carolyn Gross
Chaos & fear are closely
linked. When we shift into a panic state, we fuel the flames of chaos. I love the analogy of "fear storms," because that's
what they are & eventually they blow over just like a storm, if we don't encourage them to stay.
When our abstract, analytical
mind grabs hold of a fearful situation, we can be overwhelmed by problems in all areas. Real or imagined, these thoughts activate
all our stress hormones. Think back on a situation where you were waiting for a loved one to arrive & when he or she failed
to show up, you began thinking the worst. Suddenly your whole being became upset, restless & fitful & the tension
lasted until your fears were proved unfounded. Sound familiar? When these fear storms take over we're completely out of the
moment.
Our aging process speeds up
during stressful, sleepless & frustrated times in our lives. When the fear storms hit hard, we need to apply damage control
when they finally move on. We need to counter the aging process that kicks into gear when we advance ourselves at the cost
of another or let the chaos of others rule our lives.
Left & Right-Brain Functions
During Stress When we are in the midst of chaos, our right brain functioning shuts off & we rely solely on our
left-brain. Look at the qualities of left-brain & right-brain activity:
LEFT BRAIN
RIGHT BRAIN
Language Linear Logical Digital Abstract Concrete Reason Analytical Music-Beat Sequential Time-bound
Some people will be more attracted
to right brain versus left-brain characteristics, but we need both. What happens during stress & overload is that the
attributes of the right brain become inaccessible, which means we lose our intuitiveness & imagination. The way to bridge
back over to our holistic right brain is to find the calm in the midst of the storm.
Those aggravating things
that go wrong in the day & those irritating things that go bump in the night – disrupting routines & interrupting
sleep – all have a cumulative effect on your brain, especially its ability to remember & learn.
As science gains greater insight into the consequences of stress on the brain, the picture that emerges isn't a pretty one. A chronic overreaction
to stress overloads the brain with powerful hormones that are intended only for short-term duty in emergency situations. Their cumulative effect damages & kills brain cells.
How Your Brain Responds to Stress
Did you know that the emotional
& physical responses you have to stress are set in motion by a series of chemical releases & reactions? Find out what is really going on inside your body &
why not all stress is bad.
“Attack of the Adrenals”- A Metabolic
Story
The ambulance siren screams
it’s warning to get out of the way. You can’t move your car because you’re stuck in a bumper-to-bumper traffic
jam that reaches as far as the eye can see. There must be an accident up ahead. Meanwhile the road construction crew a few
feet from your car is jack-hammering the pavement. You're about to enter the stress zone.
Inside your body the alert goes out.
"Attention all parasympathetic forces.
Urgent. Adrenal gland missile silos mounted atop kidneys have just released chemical cortisol
weapons of brain destruction. Mobilize all internal defenses. Launch immediate counter-calm hormones before hippocampus is
hammered by cortisol."
Hormones rush to your adrenal
glands to suppress the streaming cortisol on its way to your brain. Other hormones rush
to your brain to round up all the remnants of cortisol missles that made it to your hippocampus.
These hormones escort the cortisol remnants back to Kidneyland for a one-way ride on the
Bladderhorn. You have now reached metabolic equilibrium, also known as homeostasis.
Inside Homeostasis
When a danger finally passes
or the perceived threat is over, your brain initiates a reverse course of action that releases a different bevy of biochemicals
throughout your body.
Attempting to
bring you back into balance, your brain seeks the holy grail of "homeostasis," that elusive
state of metabolic equilibrium between the stimulating & the tranquilizing chemical forces in your body.
If either
the one of the stimulating or tranquilizing chemical forces dominates the other without relief, then you'll
experience an on-going state of internal imbalance. This condition is known as stress. And it can have serious consequences for your brain cells.
Parasympathetic & Sympathetic Nervous System
The sympathetic
nervous system (SNS) turns on the fight or flight response. In contrast, the parasympathetic nervous system (PNS) promotes the relaxation response.
Like two tug-of-war teams
skillfully supporting their rope with a minimum of tension, the SNS & PNS carefully maintain metabolic equilibrium by
making adjustments whenever something disturbs this balance.
The strongmen on these teams
are hormones, the chemical messengers produced by endocrine glands. Named after a Greek word meaning "to set in motion," hormones travel thru the bloodstream to accelerate or suppress metabolic functions.
The trouble is that some stress hormones don't know when to quit pulling. They remain active in the brain for too
long – injuring & even killing cells in the hippocampus, the area of your brain needed for memory & learning.
Because of this hierarchical
dominance of the SNS over the PNS, it often requires conscious effort to initiate your relaxation response & reestablish
metabolic equilibrium.
The Emotional Brain- Limbic System
The primary area of the brain
that deals with stress is its limbic system. Because of its enormous influence on emotions & memory, the limbic system
is often referred to as the emotional brain. It's also called the mammalian brain, because it emerged with the evolution with
our warm-blooded relatives & marked the beginning of social cooperation in the animal kingdom.
Whenever you perceive a threat,
imminent or imagined, your limbic system immediately responds via your autonomic nervous system – the complex network
of endocrine glands that automatically regulates metabolism.
The term "stress" is short
for distress, a word evolved from Latin that means "to draw or pull apart." The Romans even used the term districtia to describe
"a being torn asunder." When stressed-out, most of us can probably relate to this description.
Distress Signals from Your Brain
Your sympathetic nervous system
does an excellent job of rapidly preparing you to deal with what's perceived as a threat to your safety. Its hormones initiate
several metabolic processes that best allow you to cope with sudden danger.
Your adrenal glands release
adrenaline (also known as epinephrine) & other hormones that increase breathing, heart rate, & blood pressure. This
moves more oxygen-rich blood faster to the brain & to the muscles needed for fighting or fleeing. And, you have plenty
of energy to do either, because adrenaline causes a rapid release of glucose & fatty acids into your bloodstream. Also,
your senses become keener, your memory sharper & you're less sensitive to pain.
Other hormones shut down functions
unnecessary during the emergency. Growth, reproduction & the immune system all go on hold. Blood flow to the skin is reduced.
That's why chronic stress leads to sexual dysfunction, increases your chances of getting sick, & often manifests as skin
ailments.
With your mind & body
in this temporary state of metabolic overdrive, you're now prepared to respond to a life-threatening situation.
Whole-brain Circuit Map Could Reveal What Goes Wrong In Autism, Schizophrenia And Other Brain
Disorders
ScienceDaily (Apr. 3, 2009) — Thirty-seven scientists
from Cold Spring Harbor Laboratory (CSHL) and 20 other major research institutions in the U.S. and Europe have issued a major
challenge to the neuroscience community. At long last, the time has come, they argue in a just- published paper, to assemble
a comprehensive map of the major neural circuits in the mammalian brain.
In an age in which the genomes of many organisms, including
that of humans, have been fully sequenced and can be accessed instantly by anyone with a computer, anywhere in the world,
it is astonishing to consider that "we have, as yet, not been able to compile a whole-brain map of the circuitry that underlies
the functioning of our own brains," notes Professor Partha P. Mitra, Ph.D., senior author of the paper and leader of the ongoing
Brain Architecture Project at CSHL, funded by the WM Keck Foundation. To help address this knowledge gap, Mitra organized
a series of meetings at the CSHL Banbury Center in 2007 and 2008, from which this proposal grew.
The neuroscience community's "sparse knowledge" of mammalian
neuroanatomical circuitry is "perhaps the largest lacuna in our knowledge about nervous system structure," Mitra and colleagues
observe in their paper, which appears in the March issue of PLoS Computational Biology.
The case for committing resources to assembly of a whole-brain
circuit map is particularly strong, they say, because it almost certainly will provide insights about what goes wrong in brain
dysfunctions spanning a range of neurodevelopmental illnesses including autism, schizophrenia, and perhaps mood disorders
such as depression, bipolar illness, and obsessive-compulsive disorder (OCD). Further, the authors argue that technological
advances along with decreasing computational and data-storage costs have made such an effort feasible now, when it could only
be dreamt of even in the recent past.
A community-wide project to prepare a 'first draft'
Mitra and his co-authors therefore advocate for "a concerted
effort" to complete a first-draft circuit map of the entire mouse brain within two to three years, as a first step to mapping
vertebrate brain architecture across species. The proposed project would ideally be pursued simultaneously by neuroscientists
at multiple institutions according to standardized protocols. "In this respect," says Jason Bohland, Ph.D., a postdoctoral
neuroscience researcher at CSHL and the paper's lead author, "it would be analogous to the multi-institution effort to sequence
the human genome, with the important distinction that our brain-circuit map could be completed much more rapidly and would
cost a small fraction of the genome project – as little as a few million dollars ranging up to perhaps $20 million,
depending on the redundancy in coverage that we commit to."
To date, research on the brains of mammals – typically,
rodents and non-human primates – has described, using a multitude of different techniques, only a small fraction of
the total set of neuronal pathways, in an unsystematic manner. Although spectacular advances have been made in neuroscientists'
ability to examine and measure the output of individual neurons in the brains of living animals, such studies have shed little
light on how the brain as a whole is wired together. In much the same way that the study of the genome has shifted to emphasize
networks of interacting genes, neuroscientists are beginning to understand the importance of circuit-level properties in the
normal and dysfunctional brain.
This, says Mitra, is notable in part because "the defining architectural
feature of the nervous system is precisely that it forms a circuit." One critical question, therefore, is at what level of
resolution to attempt a whole-brain circuit diagram. Mitra and co-authors are proposing to map the circuit in the mouse brain
at what they call a "mesoscopic scale." Somewhere between the micro and macroscopic, this intermediate level corresponds with
the basic architectural organization of the mouse brain, in terms of its observed cellular, chemical, and genetic makeup.
Most importantly, the authors expect this to be the level at which the pattern of connections in individual animals will have
a significant degree of commonality, ultimately providing a meaningful and tractable description of the brain's structure.
Tracing the inputs and outputs of each area
Brain organization at the macroscopic level – the level
of entire structural-functional systems and major nerve-fiber bundles – is somewhat understood, but provides an insufficient
level of description of the overall wiring diagram. Some scientists have argued that it would be best to map mouse brain structure
at the micro-level of individual synapses – the myriad gaps across which individual neurons communicate, with the help
of neurotransmitters and modulators such as glutamate, GABA, acetylcholine, dopamine and serotonin. But this isn't technologically
feasible to do on a brain-wide scale for a mouse, let alone larger vertebrate brains. Data storage at such a scale, which
would involve storing nanometer-resolution images made with electron microscopes, could cost as much as one billion dollars,
Mitra says.
In contrast, the proposed project is "both technologically and
economically practical, involving techniques that are well proven," according to Mitra. All measurements will be made in standard
lab mice of precisely the same developmental age – 56 days, as in the Allen Brain Atlas project; each mouse will be
injected in one brain area with one or more tracers, which are actively transported within individual nerve cells. These tracers
may be "conventional" molecules that have been used by neuroanatomists over the last several decades, or engineered viruses
that infect cells at the injection site, marking their extent through the expression of a fluorescent protein. The utility
of these techniques is in tracing projection neurons either from axon terminals to potentially distant cell bodies or vice-versa.
Together, the tracers will provide a view of the pattern of
inputs and outputs for a given site in the brain. These patterns will be mapped from images of thinly sectioned brain slices
obtained using light microscopy, taking advantage of recently available technologies to rapidly and automatically scan and
digitize a set of slides.
Extracting and combining the results across individual mice
will be a computational challenge that requires automating many of the steps that neuroanatomists now perform by hand. Bohland
is aware of these challenges. "Solving these problems in general is difficult because the circumstances of individual experiments
can be wildly different," he acknowledges, "But in the systematic, standardized protocols we call for, finding solutions becomes
considerably easier."
The full dataset will comprise hundreds of terabytes –
a very modest data-storage burden, according to Mitra. "That will give us about twofold coverage of the entire brain circuit
in a first draft, and could be accomplished in two or three years, with cooperation from the neuroscience community. At more
robust funding levels, we could attempt 10-fold coverage over, perhaps, a five-year period." In the spirit of genome projects,
all data from the proposed program would be made rapidly available over the web to the entire research community.
While the immediate focus now is to bring a mouse connectivity
project to fruition, the authors also make the case for cataloging and digitizing results from existing studies in other species,
and for filling key gaps with targeted studies. Moreover, there is an important need, they argue, for further development
and validation of experimental techniques that can be used directly in the human brain.
Comparing circuits in healthy brain vs. the brain in autism
or schizophrenia
Perhaps the most exciting aspect of such a brain mapping project
is its likelihood to deepen our understanding of what goes awry at the circuit level in neuropsychiatric illnesses. At present,
scientists are lacking data of this type with which to work on theories of disease causation and mechanism. "In recent years,"
Mitra observes, "many scientists have made mouse models of various complex disorders, such as schizophrenia or autism. But
so far no one has been able to pinpoint what goes wrong in brain circuitry when you have one of these devastating illnesses.
"It has been hypothesized, at least for neurodevelopmental disorders,
that the circuit is altered during the developmental process, in some manner fundamentally changing the circuit. Once we have
succeeded in fully mapping the brain in the healthy mouse, we will be able to measure, objectively, how the whole-brain circuit
differs in mice that model various aspects of behaviors or known genetic alterations associated with human illnesses like
autism or schizophrenia.
"I think this would be a crucial missing piece in any effort
to understand comparatively, not at the level of observed behavior, or at the level of the genome, but at the level of the
brain circuit, how healthy individuals differ from those with illness," Mitra says. "With a circuit map we will be able to
hypothesize disease-circuit phenotypes for neurodevelopmental illnesses, which, in turn, should lead to new understanding
of disease causation and mechanism, and to the development of new therapeutic approaches.
"Our first challenge, however, is to engage our neuroscience
colleagues and enlist them in the project to get a first draft of the healthy mouse brain. That's the necessary first step
before we can begin looking at brain circuits in disease and making comparisons."
please have a great day & take a few minutes to explore some of the
other sites in the emotional feelings network of sites! explore
the unresolved emotions & feelings that may be the cause of some of your pain & hurt... be curious & open to new
possibilities! thanks again for visiting at anxieties 102!
