[Paleopsych] what it means to have guts
HowlBloom at aol.com
HowlBloom at aol.com
Fri Jan 20 22:42:56 UTC 2006
Put the following two articles together and you get this pair of
conclusions:
1. the protein stathmin kicks fear into high gear and
2. the protein gastrin stops fear in its tracks.
Gastrin is a protein from the intestines, a protein involved in having a
good meal. So does being well-fed stop fear—does it make you fearless?
The folks who made up our clichés may have been more accurate than they knew
when they said that people who are fearless “have guts.”
By the way, I’ve been looking for the stress-handling system in the brain
for the last decade. It looks as if the stathmin and gastrin system may be a
part of it. When I came down with Chronic Fatigue Syndrome in 1988, my
stress-handling system seemingly lost its inhibitory abilities and ramped up my
stress sensitivity beyond all imagining. Was I overloaded with stathmin and
stripped of gastrin?
________
Retrieved November 18, 2005, from the World Wide Web
http://www.newscientist.com/article.ns?id=dn8337
Gene turn-off makes meek mice fearless * 17:00 17 November 2005 *
NewScientist.com news service Deactivating a specific gene transforms meek mice into
daredevils, researchers have found. The team believe the research might one
day enable people suffering from fear – in the form of phobias or anxiety
disorders, for example – to be clinically treated.
The research found that mice lacking an active gene for the protein stathmin
are not only more courageous, but are also slower to learn fear responses to
pain-associated stimuli, says geneticist Gleb Shumyatsky, at Rutgers
University in New Jersey, US. In the experiments, the stathmin-lacking mice
wandered out into the centre of an open box, in defiance of the normal mouse
instinct to hide along the box’s walls to avoid potential predators. And to test
learned fear, the mice were exposed to a loud sound followed by a brief
electric shock from the floor below them. A day later, normal mice froze when the
sound was played again. Stathmin-lacking mice barely reacted to the sound at
all. Neural responses In both mice and humans, the amygdala area of the
brain serves as the control centre of basic fear impulses. Stathmin is found
almost exclusively in this and related brain areas. The protein is known to
destabilise microtubule structures that help maintain the connections between
neurons. This allows the neurons to make new connections, allowing the animal to
learn and process fear experiences, Shumyatsky says. Without it, the neural
responses are stilted. The lack of the protein does not appear to affect
other learning experiences, as both sets of mice were able to memorise the
paths out of mazes equally well. “This is a good sign for an eventual clinical
application that could let people deal with their fears in an entirely
different way,” Shumyatsky says. In 2002, Shumyatsky and colleagues published a
study on a similar gene encoding for a protein called GRP. But this protein seems
only to be associated with learned fear, and would therefore only have
clinical implications for conditions such as post-traumatic stress disorder.
Stathmin, on the other hand, seems to affect both learned and innate fear, which
could lead to treatments for a much broader range of phobias and anxiety
disorders, Shumyatsky says. Journal reference: Cell (DOI:
10.1016/j.cell.2005.08.038) Printable version Email to a friend RSS Feed Cover of latest issue of
New
_________
Site: ScienceDaily Magazine Page URL:
http://www.sciencedaily.com/releases/2002/12/021213062425.htm Original Source: Howard Hughes Medical Institute
Date Posted: 12/13/2002 Researchers Discover Gene That Controls Ability To
Learn Fear Researchers have discovered the first genetic component of a
biochemical pathway in the brain that governs the indelible imprinting of fear-related
experiences in memory. The gene identified by researchers at the Howard
Hughes Medical Institute at Columbia University encodes a protein that
inhibits the action of the fear-learning circuitry in the brain. Understanding how
this protein quells fear may lead to the design of new drugs to treat
depression, panic and generalized anxiety disorders. The findings were reported in
the December 13, 2002 issue of the journal Cell, by a research team that
included Howard Hughes Medical Institute (HHMI) investigators Eric Kandel at
Columbia University and Catherine Dulac at Harvard University. Lead author of the
paper was Gleb Shumyatsky, a postdoctoral fellow in Kandel's laboratory at
Columbia University. Other members of the research team are at the National
Institutes of Health and Harvard Medical School. According to Kandel,
earlier studies indicated that a specific signaling pathway controls fear-related
learning, which takes place in a region of the brain called the amygdala.
"Given these preliminary analyses, we wanted to take a more systematic approach
to obtain a genetic perspective on learned fear," said Kandel. One of the
keys to doing these genetic analyses, Kandel said, was the development of a
technique for isolating and comparing the genes of individual cells, which was
developed at Columbia by Dulac with HHMI investigator Richard Axel.
Shumyatsky applied that technique, called differential screening of single-cell cDNA
libraries, to mouse cells to compare the genetic activity of cells from a
region of the amygdala called the lateral nucleus, with cells from another region
of the brain that is not known to be involved in learned fear. The
comparison revealed two candidate genes for fear-related learning that are highly
expressed in the amygdala. The researchers decided to focus further study on one
of the genes, Grp, which encodes a short protein called gastrin-releasing
peptide (GRP), because they found that this protein has an unusual distribution
in the brain and is known to serve as a neurotransmitter. Shumyatsky's
analysis revealed that the Grp gene was highly enriched in the lateral nucleus,
and in other regions of the brain that feed auditory inputs into the amygdala.
"Gleb's finding that this gene was active not only in the lateral nucleus
but also in a number of regions that projected into the lateral nucleus was
interesting because it suggested that a whole circuit was involved," said
Kandel. Shumyatsky next showed that GRP is expressed by excitatory principal
neurons and that its receptor, GRPR, is expressed by inhibitory interneurons. The
researchers then undertook collaborative studies with co-author Vadim
Bolshakov at Harvard Medical School to characterize cells in the amygdala that
expressed receptors for GRP. Those studies in mouse brain slices revealed that
GRP acts in the amygdala by exciting a population of inhibitory interneurons
in the lateral nucleus that provide feedback and inhibit the principal
neurons.
The researchers next explored whether eliminating GRP's activity could
affect the ability to learn fear by studying a strain of knockout mice that lacked
the receptor for GRP in the brain. In behavioral experiments, they first
trained both the knockout mice and normal mice to associate an initially
neutral tone with a subsequent unpleasant electric shock. As a result of the
training, the mouse learns that the neutral tone now predicts danger. After the
training, the researchers compared the degree to which the two strains of mice
showed fear when exposed to the same tone alone -- by measuring the duration
of a characteristic freezing response that the animals exhibit when fearful.
"When we compared the mouse strains, we saw a powerful enhancement of learned
fear in the knockout mice," said Kandel. Also, he said, the knockout mice
showed an enhancement in the learning-related cellular process known as
long-term potentiation. "It is interesting that we saw no other disturbances in
these mice," he said. "They showed no increased pain sensitivity; nor did they
exhibit increased instinctive fear in other behavioral studies. So, their
defect seemed to be quite specific for the learned aspect of fear," he said.
Tests of instinctive fear included comparing how both normal and knockout mice
behaved in mazes that exposed them to anxiety-provoking environments such as
open or lighted areas. "These findings reveal a biological basis for what had
only been previously inferred from psychological studies -- that instinctive
fear, chronic anxiety, is different from acquired fear," said Kandel. In
additional behavioral studies, the researchers found that the normal and
knockout mice did not differ in spatial learning abilities involving the
hippocampus, but not the amygdala, thus genetically demonstrating that these two
anatomical structures are different in their function. According to Kandel, further
understanding of the fear-learning pathway could have important implications
for treating anxiety disorders. "Since GRP acts to dampen fear, it might be
possible in principle to develop drugs that activate the peptide,
representing a completely new approach to treating anxiety," he said. However, he
emphasized, the discovery of the action of the Grp gene is only the beginning of a
long research effort to reveal the other genes in the fear-learning pathway.
More broadly, said Kandel, the fear-learning pathway might provide an
invaluable animal model for a range of mental illnesses. "Although one would
ultimately like to develop mouse models for various mental illnesses such as
schizophrenia and depression, this is very hard to do because we know very little
about the biological foundations of most forms of mental illness," he said.
"However, we do know something about the neuroanatomical substrates of anxiety
states, including both chronic fear and acute fear. We know they are centered
in the amygdala. "And while I don't want to overstate the case, in studies
of fear learning we could well have an excellent beginning for animal models
of a severe mental illness. We already knew quite a lot about the neural
pathways in the brain that are involved in fear learning. And now, we have a way
to understand the genetic and biochemical mechanisms underlying those
pathways." Editor's Note: The original news release can be found here. Note: This
story has been adapted from a news release issued for journalists and other
members of the public. If you wish to quote from any part of this story,
please credit Howard Hughes Medical Institute as the original source.
----------
Howard Bloom
Author of The Lucifer Principle: A Scientific Expedition Into the Forces of
History and Global Brain: The Evolution of Mass Mind From The Big Bang to the
21st Century
Recent Visiting Scholar-Graduate Psychology Department, New York University;
Core Faculty Member, The Graduate Institute
www.howardbloom.net
www.bigbangtango.net
Founder: International Paleopsychology Project; founding board member: Epic
of Evolution Society; founding board member, The Darwin Project; founder: The
Big Bang Tango Media Lab; member: New York Academy of Sciences, American
Association for the Advancement of Science, American Psychological Society,
Academy of Political Science, Advanced Technology Working Group, Human Behavior
and Evolution Society, International Society for Human Ethology; advisory
board member: Institute for Accelerating Change ; executive editor -- New
Paradigm book series.
For a peek into the ultimate cross-disciplinary field, Omnology, see
http://bigbangtango.net/website/omnology.html
For information on The International Paleopsychology Project, see:
www.paleopsych.org
for two chapters from
The Lucifer Principle: A Scientific Expedition Into the Forces of History,
see www.howardbloom.net/lucifer
For information on Global Brain: The Evolution of Mass Mind from the Big
Bang to the 21st Century, see www.howardbloom.net
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