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<DIV><SPAN class=167312418-21012006>The stress-handling system may not be in the
brain brain.</SPAN></DIV>
<DIV><SPAN class=167312418-21012006>It may be in the heart brain or stomach
brain.</SPAN></DIV>
<DIV><SPAN class=167312418-21012006></SPAN> </DIV>
<DIV><SPAN class=167312418-21012006>Steve H.</SPAN></DIV>
<BLOCKQUOTE dir=ltr style="MARGIN-RIGHT: 0px">
<DIV class=OutlookMessageHeader dir=ltr align=left><FONT face=Tahoma
size=2>-----Original Message-----<BR><B>From:</B>
paleopsych-bounces@paleopsych.org
[mailto:paleopsych-bounces@paleopsych.org]<B>On Behalf Of
</B>HowlBloom@aol.com<BR><B>Sent:</B> Friday, January 20, 2006 2:43
PM<BR><B>To:</B> paleopsych@paleopsych.org<BR><B>Subject:</B> [Paleopsych]
what it means to have guts<BR><BR></FONT></DIV><FONT id=role_document
face=Arial size=3>
<DIV>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">Put the following two articles together and you get
this pair of conclusions:<SPAN style="mso-spacerun: yes">
</SPAN><o:p></o:p></FONT></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p><FONT
face="Times New Roman"> </FONT></o:p></SPAN></P>
<OL style="MARGIN-TOP: 0in" type=1>
<LI class=MsoNormal
style="MARGIN: 0in 0in 0pt; mso-list: l0 level1 lfo1; tab-stops: list .5in"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">the protein stathmin kicks fear<SPAN
style="mso-spacerun: yes"> </SPAN>into high gear and
<o:p></o:p></FONT></SPAN>
<LI class=MsoNormal
style="MARGIN: 0in 0in 0pt; mso-list: l0 level1 lfo1; tab-stops: list .5in"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">the protein gastrin stops fear in its tracks.
<o:p></o:p></FONT></SPAN></LI></OL>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p><FONT
face="Times New Roman"> </FONT></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">Gastrin is a protein from the intestines, a protein
involved in having a good meal.<SPAN style="mso-spacerun: yes">
</SPAN>So does being well-fed stop fear—does it make you fearless?<SPAN
style="mso-spacerun: yes"> </SPAN><o:p></o:p></FONT></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p><FONT
face="Times New Roman"> </FONT></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">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.”<o:p></o:p></FONT></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p><FONT
face="Times New Roman"> </FONT></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">By the way, I’ve been looking for the stress-handling
system in the brain for the last decade.<SPAN style="mso-spacerun: yes">
</SPAN>It looks as if the stathmin and gastrin system may be a part of
it.<SPAN style="mso-spacerun: yes"> </SPAN>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.<SPAN style="mso-spacerun: yes"> </SPAN>Was I overloaded with
stathmin and stripped of gastrin?<o:p></o:p></FONT></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">________<o:p></o:p></FONT></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT face="Times New Roman"
size=2>Retrieved <SPAN style="mso-no-proof: yes">November 18, 2005</SPAN>,
from the World Wide Web<SPAN style="mso-spacerun: yes">
</SPAN>http://www.newscientist.com/article.ns?id=dn8337 </FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT face="Times New Roman"
size=2>Gene turn-off makes meek mice fearless<SPAN
style="mso-spacerun: yes"> </SPAN>* <st1:time Minute="0"
Hour="17">17:00</st1:time> <st1:date Year="2005" Day="17" Month="11">17
November 2005</st1:date> * 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.</FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=2><FONT
face="Times New Roman"><SPAN style="mso-spacerun: yes"> </SPAN>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.<SPAN style="mso-spacerun: yes"> </SPAN>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.<SPAN style="mso-spacerun: yes">
</SPAN>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<SPAN
style="mso-spacerun: yes"> </SPAN>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.<SPAN
style="mso-spacerun: yes"> </SPAN>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.<SPAN style="mso-spacerun: yes"> </SPAN>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.<SPAN
style="mso-spacerun: yes"> </SPAN>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.<SPAN style="mso-spacerun: yes">
</SPAN><B style="mso-bidi-font-weight: normal">Stathmin,</B> 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.<SPAN style="mso-spacerun: yes"> </SPAN>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 </FONT></FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p><FONT
face="Times New Roman"> </FONT></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><FONT
face="Times New Roman">_________<o:p></o:p></FONT></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=2><FONT
face="Times New Roman">Site:<SPAN style="mso-spacerun: yes">
</SPAN>ScienceDaily Magazine Page URL:
http://www.sciencedaily.com/releases/2002/12/021213062425.htm<SPAN
style="mso-spacerun: yes"> </SPAN>Original Source: Howard Hughes Medical
Institute Date Posted: <st1:date Year="2002" Day="13"
Month="12">12/13/2002</st1:date> Researchers Discover Gene That Controls
Ability To Learn Fear <B>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.</B> <B><SPAN
style="mso-spacerun: yes"> </SPAN>The gene</B> identified by researchers
at the Howard Hughes Medical Institute at
<st1:place><st1:PlaceName>Columbia</st1:PlaceName>
<st1:PlaceType>University</st1:PlaceType></st1:place> <B>encodes a protein
that inhibits the action of the fear-learning circuitry in the brain.</B>
Understanding how this protein quells fear may lead to the design of new drugs
to treat depression, panic and generalized anxiety disorders.<SPAN
style="mso-spacerun: yes"> </SPAN>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
<st1:place><st1:PlaceName>Columbia</st1:PlaceName>
<st1:PlaceType>University</st1:PlaceType></st1:place>. Other members of the
research team are at the National Institutes of Health and
<st1:place><st1:PlaceName>Harvard</st1:PlaceName>
<st1:PlaceName>Medical</st1:PlaceName>
<st1:PlaceType>School</st1:PlaceType></st1:place>.<SPAN
style="mso-spacerun: yes"> </SPAN>According to Kandel, earlier studies
indicated that a specific signaling pathway controls <B>fear-related
learning</B>, which <B>takes place in</B> a region of the brain called <B>the
amygdala.</B> "Given these preliminary analyses, we wanted to take a more
systematic approach to obtain a genetic perspective on learned fear," said
Kandel.<SPAN style="mso-spacerun: yes"> </SPAN>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
<st1:City><st1:place>Columbia</st1:place></st1:City> 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.<SPAN
style="mso-spacerun: yes"> </SPAN>The researchers decided to focus
further study on <B>one of the genes, Grp, which encodes a short protein
called gastrin-releasing peptide (GRP),</B> because they found that <B>this
protein has an unusual distribution in the brain and is known to serve as a
neurotransmitter. </B>Shumyatsky's analysis revealed that <B>the Grp gene was
highly enriched in the lateral nucleus, and in other regions of the brain that
feed auditory inputs into the amygdala.</B><SPAN
style="mso-spacerun: yes"> </SPAN><B>"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,"</B> said Kandel. Shumyatsky next showed that
<B>GRP is expressed by excitatory principal neurons and that its receptor,
GRPR, is expressed by inhibitory interneurons.</B> The researchers then
undertook collaborative studies with co-author Vadim Bolshakov at
<st1:place><st1:PlaceName>Harvard</st1:PlaceName>
<st1:PlaceName>Medical</st1:PlaceName>
<st1:PlaceType>School</st1:PlaceType></st1:place> to characterize cells in the
amygdala that expressed receptors for GRP. Those studies in mouse brain slices
revealed that <B>GRP acts in the amygdala by exciting a population of
inhibitory interneurons in the lateral nucleus that provide feedback and
inhibit the principal neurons.<o:p></o:p></B></FONT></FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=2><FONT
face="Times New Roman"><SPAN style="mso-spacerun: yes"> </SPAN>The
researchers next explored whether eliminating GRP's activity could affect the
ability to learn fear by studying a strain of <B>knockout mice that lacked the
receptor for GRP in the brain</B>.<SPAN style="mso-spacerun: yes">
</SPAN>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.<SPAN
style="mso-spacerun: yes"> </SPAN>"When we compared the mouse strains,
<B>we saw a powerful enhancement of learned fear in the knockout mice,"</B>
said Kandel. Also, he said, the knockout mice showed an enhancement in the
learning-related cellular process known as long-term potentiation.<SPAN
style="mso-spacerun: yes"> </SPAN>"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.<SPAN
style="mso-spacerun: yes"> </SPAN>"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.<SPAN style="mso-spacerun: yes"> </SPAN>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.<SPAN style="mso-spacerun: yes">
</SPAN>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.<SPAN style="mso-spacerun: yes">
</SPAN>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.<SPAN style="mso-spacerun: yes"> </SPAN>"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."<SPAN
style="mso-spacerun: yes"> </SPAN>Editor's Note: The original news
release can be found here.<SPAN style="mso-spacerun: yes"> </SPAN>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.<SPAN
style="mso-spacerun: yes"> </SPAN></FONT></FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><o:p><FONT
face="Times New Roman" size=2> </FONT></o:p></P></DIV>
<DIV> </DIV>
<DIV><FONT lang=0 face=Arial size=2 PTSIZE="10"
FAMILY="SANSSERIF">----------<BR>Howard Bloom<BR>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<BR>Recent Visiting Scholar-Graduate Psychology Department, New York
University; Core Faculty Member, The Graduate
Institute<BR>www.howardbloom.net<BR>www.bigbangtango.net<BR>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.<BR>For a peek into the ultimate cross-disciplinary
field, Omnology, see http://bigbangtango.net/website/omnology.html<BR>For
information on The International Paleopsychology Project, see:
www.paleopsych.org<BR>for two chapters from <BR>The Lucifer Principle: A
Scientific Expedition Into the Forces of History, see
www.howardbloom.net/lucifer<BR>For information on Global Brain: The Evolution
of Mass Mind from the Big Bang to the 21st Century, see
www.howardbloom.net<BR></FONT></DIV></BLOCKQUOTE></FONT></BODY></HTML>