[Paleopsych] if neurons sing the melody, do astrocytes sing bass?

[HowlBloom at aol.com]

Eshel Ben-Jacob has been writing about the role of glial tissue in the brain 
and has proposed that it carries out an unusual function—a form of group 
communication, mass-mood-summation, keeper of the zeitgeist of the neuronal 
community, or, to put it more technically and far-less precisely, a part of the brain’
s quorum-sensing machinery.  
 
Eshel has said that the brain is not the only mass of cells that uses this 
sort of across-cell-summarizer, this sort of sense of mass-hungers and of the 
greater good.  The gel secreted by a bacterial colony, the gel upon which it 
sits, does, Eshel says, the same sort of thing—carrying the common zeitgeist from 
end to end of the colony.  The big difference may be this.  A brain is a 
community of one hundred billion cells.  A bacterial colony is often a community 
of a trillion or more.
 
Below is an article that supports Eshel’s vision (if I’ve expressed it 
correctly) of the role of the brain’s glial fabric.  
 
Ps Bear with me while I toss another metaphor at you.  If the neurons of the 
brain sing the melody, the glial tissue may sing the bass.  The bass section 
is the rhythm section—the section that determines the pace and that coordinates 
of the harmonies and discords of the choir.
 
Howard
Retrieved August 1, 2004, from the World Wide Web 
http://web12.epnet.com/citation.asp?tb=1&_ug=sid+F74E62A1%2D7A66%2D4AC6%2D9CA7
%2DA3DBEAB5C3BD%40sessionmgr5+dbs+aph+cp+1+11CB&_us=hs+True+cst+0%3B2+or+Date+
ss+SO+sm+KS+sl+0+dstb+KS+ri+KAAACBUB00000781+2237&_uso=tg%5B0+%2D+db%5B0+%2Dap
h+hd+False+clv%5B1+%2DScientific++American+clv%5B0+%2D20040400%2D20040400+op%5
B0+%2D+cli%5B1+%2DSO+cli%5B0+%2DDT1+st%5B0+%2Dglia+ex%5B0+%2Dproximity+F488&cf
=1&fn=1&rn=1
The Other Half of the Brain ,  By: Fields, R. Douglas, Scientific American, 
00368733, Apr2004, Vol. 290, Issue 4 Database: Academic Search Premier  The 
Other Half of the Brain  Contents See Me, Hear Me Gila Communicating with Glia 
ATP Is the Messenger Axons Control Glia's Fate Outside the Neuronal Box MORE TO 
EXPLORE Overview/Glia  MOUNTING EVIDENCE SUGGESTS THAT GLIAL CELLS, OVERLOOKED 
FOR HALF A CENTURY, MAY BE NEARLY AS CRITICAL TO THINKING AND LEARNING AS 
NEURONS ARE  The recent book Driving Mr. Albert tells the true story of 
pathologist Thomas Harvey, who performed the autopsy of Albert Einstein in 1955. After 
finishing his task, Harvey irreverently took Einstein's brain home, where he 
kept it floating in a plastic container for the next 40 years. From time to 
time Harvey doled out small brain slices to scientists and pseudoscientists 
around the world who probed the tissue for clues to Einstein's genius. But when 
Harvey reached his 80s, he placed what was left of the brain in the trunk of his 
Buick Skylark and embarked on a road trip across the country to return it to 
Einstein's granddaughter.  One of the respected scientists who examined 
sections of the prized brain was Marian C. Diamond of the University of California at 
Berkeley. She found nothing unusual about the number or size of its neurons 
(nerve cells). But in the association cortex, responsible for high-level 
cognition, she did discover a surprisingly large number of nonneuronal cells known 
as glia--a much greater concentration than that found in the average Albert's 
head.  An odd curiosity? Perhaps not. A growing body of evidence suggests that 
glial cells play a far more important role than historically presumed. For 
decades, physiologists focused on neurons as the brain's prime communicators. 
Glia, even though they outnumber nerve cells nine to one, were thought to have 
only a maintenance role: bringing nutrients from blood vessels to neurons, 
maintaining a healthy balance of ions in the brain, and warding off pathogens that 
evaded the immune system. Propped up by glia, neurons were free to communicate 
across tiny contact points called synapses and to establish a web of 
connections that allow us to think, remember and jump for joy.  That long-held model 
of brain function could change dramatically if new findings about gila pan out. 
In the past several years, sensitive imaging tests have shown that neurons 
and glia engage in a two-way dialogue from embryonic development through old 
age. Glia influence the formation of synapses and help to determine which neural 
connections get stronger or weaker over time; such changes are essential to 
learning and to storing long-term memories. And the most recent work shows that 
gila also communicate among themselves, in a separate but parallel network to 
the neural network, influencing how well the brain performs. Neuroscientists 
are cautious about assigning new prominence to glia too quickly, yet they are 
excited by the prospect that more than half the brain has gone largely 
unexplored and may contain a trove of information about how the mind works. See Me, 
Hear Me  THE MENTAL PICTURE most people have of our nervous system resembles a 
tangle of wires that connect neurons. Each neuron has a long, outstretched 
branch--an axon--that carries electrical signals to buds at its end. Each bud 
emits neurotransmitters--chemical messenger molecules--across a short synaptic gap 
to a twig like receptor, or dendrite, on an adjacent neuron. But packed 
around the neurons and axons is a diverse population of glial cells. By the time of 
Einstein's death, neuroscientists suspected that glial cells might contribute 
to information processing, but convincing evidence eluded them. They 
eventually demoted glia, and research on these cells slid into the backwater of 
science for a long time.  Neuroscientists failed to detect signaling among glia, 
partly because they had insufficient technology analytical but primarily because 
they were looking in tie wrong place. They incorrectly assumed that if glia 
could chatter they would use the same electrical mode of communication seen in 
neurons. That is, they would generate electrical impulses called action 
potentials that would ultimately cause the cells to release neurotransmitters across 
synapses, igniting more impulses in other neurons. Investigators did discover 
that glia had many of the same voltage-sensitive ion channels that generate 
electrical signals in axons, but they surmised that these channels merely 
allowed glia to sense indirectly the level of activity of adjacent neurons. They 
found that glial cells lacked the membrane properties required to actually 
propagate their own action potentials. What they missed, and what advanced imaging 
techniques have now revealed, is that glia rely on chemical signals instead of 
electrical ones to convey messages.  Valuable insights into how glia detect 
neuronal activity emerged by the mid-1990s, after neuroscientists established 
that glia had a variety of receptors on their membranes that could respond to a 
range of chemicals, including, in some cases, neurotranimitters. This 
discovery suggested that glia might communicate using chemical signals that neurons 
did not recognize and at limes might react directly to neurotransmitters emitted 
by neurons.  To prove such assertions, scientists first had to show that glia 
actually do "listen in" on neuronal communication and take action based on 
what they "hear'" Earlier work indicated that an influx of calcium into glial 
cells could be a sign that they had been stimulated. Based on that notion, 
investigators devised a laboratory method called calcium imaging to see whether 
glial cells known as terminal Schwann cells--. which surround synapses where 
nerves meet muscle cells--were sensitive to neuronal signals emitted at these 
junctions. The method confirmed that Schwann Cells, at least, did respond to 
synaptic firing and that the reaction involved an influx of calcium ions into the 
cells.  But were glia limited only to eavesdropping on neuronal activity, by 
scavenging traces of neurotransmitter leaking from a synapse? More 
general-function Schwann cells also surround axons all along nerves in the body, not just 
at synapses, and oligodencrocyte glia cells wrap around axons in the central 
nervous sys-tern (brain and spinal cord). At my National Institutes of Health 
lab, we wanted to know if glia could monitor neural activity anywhere as it 
flowed through axons in neural circuits. If so, how was that communication 
mediated? More important, how exactly would glia be affected by what they heard?  To 
find answers, we cultured sensory neurons (dorsal root ganglion, or DRG, 
cells) from mice in special lab dishes equipped with electrodes that would enable 
us to trigger action potentials in the axons. We added Schwann cells to some 
cultures and oligodendrocytes to others.  We needed to tap independently into 
the activity of the axons and the glia to determine if the latter were detecting 
the axon messages. We used a calcium-imaging technique to record visually 
what the cells were doing, introducing dye that fluoresces if it binds to calcium 
ions. When an axon fires, voltage-sensitive ion channels in the neuron's 
membrane open, allowing calcium ions to enter. We would therefore expect to see 
the firing as a flash of green fluorescence lighting up the entire neuron from 
the inside. As the concentration of calcium rose in a cell, the fluorescence 
would get brighter. The intensity could be measured by a photomultiplier tube, 
and images of the glowing cells could be digitized and displayed in pseudocolor 
on a monitor in real time--looking something like the radar images of 
rainstorms shown on weather reports. If glial cells heard the neuronal signals and 
did so in part by taking up calcium from their surroundings, they would light up 
as well, only later.  Staring at a computer monitor in a darkened room, my 
NIH colleague, biologist Beth Stevens, and I knew that after months of 
preparation our hypothesis was about to be tested with the flick of a switch. When we 
turned on the stimulator, the DRG neurons responded instantly, changing from 
blue to green to red and then white on a pseudocoior scale of calcium 
concentration, as calcium flooded into the axons. Initially, there were no changes in 
the Schwann cells or oligodendrocytes, but about 15 long seconds later the glia 
suddenly began to light up like bulbs on a string of Christmas lights [see 
illustration on page 59]. Somehow the cells had detected the impulse activity in 
the axons and responded by raising the concentration of calcium in their own 
cytoplasm. Gila Communicating with Glia  THUS FAR WE HAD confirmed that gila 
sense axon activity by taking in calcium. In neurons, calcium activates enzymes 
that produce neurotransmitters. Presumably, the influx in glial cells would 
also activate enzymes that would marshal a response. But what response was the 
cell attempting? More fundamentally, what exactly had triggered the calcium 
influx?  Clues came from previous work on other gliai cells in the brain known as 
astrocytes. One of their functions is to carry nutrients from capillaries to 
nerve cells; another is to maintain the optimal ionic conditions around 
neurons necessary for firing impulses. Part of the latter job is to remove excess 
neurotransmitters and ions that neurons release when they fire. In a classic 
1990 study, a group led by Stephen J. Smith of Yale University (now at Stanford 
University) used calcium imaging to show that the calcium concentration in an 
astrocyte would rise suddenly when the neurotransmitter glutamate was added to 
a cell culture. Calcium waves soon spread throughout all the astrocytes in the 
culture. The astrocytes were responding as if the neurotransmitter had just 
been released by a neuron, and they were essentially discussing the news of 
presumed neuronal firing among themselves.  Some neuroscientists wondered whether 
the communication occurred because calcium ions or related signaling 
molecules simply passed through open doorways connecting abutting astrocytes. In 1996 
S. Ben Kater and his colleagues at the University of Utah defused that 
suspicion. Using a sharp microelectrode, they cut a straight line through a layer of 
astrocytes in culture, forming a cell-free void that would act like a highway 
separating burning forests on either side. But when they stimulated calcium 
waves on one side of the break, the waves spread to astrocytes across the void 
with no difficulty. The astrocytes had to be sending signals through the 
extracellular medium, rather than through physical contact.  Intensive research in 
many laboratories over the next few year! showed similar results. Calcium 
responses could be induced in astrocytes by adding neurotransmitters or by using 
electrodes to stimulate the release of neurotransmitters from synapses. 
Meanwhile physiologists and biochemists were finding that glia had receptors for many 
of the same neurotransmitters neurons use for synaptic communication, as well 
as most of the ion channels that enable neurons to fire action potentials. ATP 
Is the Messenger  THESE AND OTHER RESULTS led to confusion. Glial 
communication is controlled by calcium influxes just as neuronal communication is. But 
electrical impulses trigger calcium changes in neurons, and no such impulse 
exists in or reaches glia. Was glial calcium influx initiated by a different 
electrical phenomenon or some other mechanism?  In their glial experiments, 
researchers were noticing that a familiar molecule kept cropping up--ATP (adenosine 
triphosphate), known to every biology student as the energy source for cellular 
activities. Although it makes a great power pack, ATP also has many features 
that make it an excellent messenger molecule between cells. It is highly 
abundant inside cells but rare outside of them. It is small and therefore diffuses 
rapidly, and it breaks down quickly. All these traits ensure that new messages 
conveyed by ATP molecules are not confused with old messages. Moreover, ATF 
is neatly packaged inside the tips of axons where neurotransmitter molecules 
are stored; it is released together with neurotransmitters at synapses and can 
travel outside synapses, too.  In 1999 Peter B. Guthrie and his colleagues at 
the University of Utah shouted conclusively that when excited, astrocytes 
release ATP into their surroundings. The ATP binds to receptors on nearby 
astrocytes, prompting ion channels to open and allow an influx of calcium. The rise 
triggers ATP release from those cells, setting off a chain reaction of AT 
mediated calcium responses across the population of astrocytes.  A model of how glia 
around an axon sense neuronal activity and then communicate to other glia 
residing at the axon's synapse was coming together. The firing of neurons somehow 
induces glial cells around an axon to emit ATP, which causes calcium intake in 
neighboring glia, prompting more ATP release, thereby activating 
communication along a string of glia that can reach far from the initiating neuron. But 
how could the glia in our experiment be detecting the neuronal firing, given 
that the axons made no synaptic, connections with the glia and the axonal gila 
were nowhere near the synapse? Neurotransmitters were not the answer; they do 
not diffuse out of axons (if they did, they could act in unintended places in 
the brain, wreaking havoc). Perhaps ATP, which is released along with 
neurotransmitters when axons fire, was somehow escaping along the axon.  To test this 
notion, we electrically stimulated pure cultures of DRG axons and then analyzed 
the medium. By exploiting the enzyme that allows fireflies to glow--a reaction 
that requires ATP--we were able to detect the release of ATP from axons by 
seeing the medium glow when axons fired. We then added Schwann cells to the 
culture and measured the calcium responses. They also lit up after axons fired an 
action potential. Yet when we added the enzyme apyrase, which rapidly destroys 
ATP-thereby intercepting the ATP before it could reach any Schwann cells--the 
glia remained dark when axons fired. The calcium response in the Schwann 
cells had been blocked, because the cells never received the ATP message.  ATP 
released from an axon was indeed triggering calcium influx into Schwann cells. 
Using biochemical analysis and digital microscopy, we also showed that the 
influx caused signals to travel from the cells' membrane to the nucleus, where the 
genes are stored, causing various genes to switch on. Amazingly, by firing to 
communicate with other neurons, an axon could instruct the readout of genes in 
a glial cell and thus influence its behavior. Axons Control Glia's Fate  TO 
THIS POINT, work by us and others had led to the conclusion that a glial cell 
senses neuronal action potentials by detecting ATP that is either released by a 
firing axon or leaked from the synapse. The gliai cell relays the message 
inside itself via calcium ions. The ions activate enzymes that release ATP to 
other glial cells or activate enzymes that control the readout of genes.  This 
insight made us wonder what functions the genes might be controlling. Were they 
telling the glia to act in ways that would influence the neurons around them? 
Stevens set out to answer this question by focusing on the process that 
prompts production of the myelin insulation around axons, which clearly would affect 
a neuron. This insulation is key to the conduction of nerve impulses at high 
speed over long distances. Its growth enables a baby to gradually hold up its 
head, and its destruction by diseases such as multiple sclerosis causes severe 
impairment.  We turned to myelin because we were curious about how an 
immature Schwann cell on an axon in the peripheral nervous system of a fetus or 
infant knows which axons will need myelin and when to start sheathing those axons 
and, alternatively, how it knows if it should transform itself into a cell that 
will not make insulation. Generally, only large-diameter axons need myelin. 
Could axon impulses or ATP release affect these decisions? We found that 
Schwann cells in culture proliferated more slowly when gathered around axons that 
were firing than around axons that were quiet. Moreover, the Schwann cells' 
development was arrested and myelin formation was blocked. Adding ATP produced the 
same effects.  Working with Vittorio Gallo and his colleagues in the adjacent 
NIH lab, however, we found a contrasting situation with the oligodendrocyte 
glia that form myelin in the brain. ATP did not inhibit their proliferation, 
but adenosine, the substance left when phosphate molecules in ATP are removed, 
stimulated the cells to mature and form myelin. The two findings indicate that 
different receptors on glia provide a clever way for a neuron to send separate 
messages to glial cells in the central or peripheral nervous system without 
having to make separate messenger molecules or specify message destinations.  
Better understanding of myelination is important. Every year thousands of 
people die and countless more are paralyzed or blinded because of demyelinating 
disease. Multiple sclerosis, for example, strikes one in 700 people. No one knows 
what exactly initiates myelinadon, but adenosine is the first substance 
derived from an axon that has been found to stimulate the process. The fact that 
adenosine is released from axons in response to axon firing means activity in 
the brain actually influences myelination. Such findings could mark paths to 
treatment. Drugs resembling adenosine might help. Adding adenosine to Stem cells 
could perhaps turn them into myelinating gila that are transplanted into 
damaged nerves. Outside the Neuronal Box  EXPERIMENTS IN OUR LAB and others 
strongly suggest that ATP and adenosine mediate the messages coursing through 
networks of Schwann and oligodendrocyte gila cells and that calcium messages are 
induced in astrocyte glia cells by ATP alone. But do glia have the power to 
regulate the functioning of neurons, other than by producing myelin?  The answer 
appears to he "yes." Richard Robitaille of the University of Montreal saw the 
voltage produced by synapses on frog muscle become stronger or weaker depending 
on what chemicals he injected into Schwann cells at the synapse. When Eric A. 
Newman of the University of Minnesota touched the retina of a rat, waves of 
calcium sent by glia changed the visual neurons' rate of firing. Studying slices 
of rat brain taken from the hippocampus--a region involved in memory--Maiken 
Nedergaard of New York Medical College observed synapses increase their 
electrical activity when adjacent astrocytes stimulated calcium waves. Such changes 
in synaptic strength are thought to be the fundamental means by which the 
nervous system changes its response through experience--a concept termed 
plasticity, suggesting that glia might play a role in the cellular basis of learning.  
One problem arises from these observations. Like a wave of cheering fans 
sweeping across a stadium, the calcium waves spread throughout the entire population 
of astrocytes. This large-scale response is effective for managing the entire 
group, but it cannot convey a very complex message. The equivalent of "Go 
team!" might be useful in coordinating general activity in the brain during the 
sleep-wake cycle or during a seizure, but local conversations are necessary if 
glial cells are to be involved in the intricacies of information processing.  
In a footnote to their 1990 paper, Smith and his colleagues stated that they 
believed neutrons and glia carried on more discrete conversations. Still, the 
researchers lacked experimental methods precise enough to deliver a. 
neurotransmitter in a way that resembled what an astrocyte would realistically 
experience at a synapse. In 2003 Philip G. Haydon of the University of Pennsylvania 
achieved this objective. He used improved laser technology to release such a 
small quantity of glutamate in a hippocampal brain slice that t would be detected 
by only a single astrocyte. Under this condition, Haydon observed that an 
astrocyte sent specific calcium signals to just a small number of nearby 
astrocytes. As Haydon put it, in addition to calcium waves that affect astrocytes 
globally, "there is short-range connectivity between astrocytes."  In other words, 
discrete astrocyte circuits in the brain coordinate activity with neuronal 
circuits. (The physical or biochemical factors that define these discrete 
astrocytic circuits are unknown at present.) Investigation by others has also 
indicated that astrocytes may strengthen signaling at synapses by secreting the same 
neurotransmitter the axon is releasing--in effect, amplifying the signal.  The 
working hypothesis that Haydon and I, along with our colleagues, are reaching 
from these discoveries is that communication among astrocytes helps to 
activate neurons whose axons terminate relatively far away and that this activity, 
in turn, contributes to the release of neurotransmitters at distant synapses. 
This action would regulate how susceptible remote synapses are to undergoing a 
change in strength, which is the cellular mechanism underlying learning and 
memory.  Results announced at the Society for Neuroscience's annual meeting in 
November 2003 support this notion and possibly expand the role of glia to 
include participation in the formation of new synapses [see box on opposite page]. 
Some of the findings build on research done two years earlier by Ben A. 
Barres, Frank W. Pfrieger and their colleagues at Stanford, who reported that rat 
neurons grown in culture made more synapses when in the presence of astrocytes.  
Working in Barres's lab, postdoctoral students Karen S. Christopherson and 
Erik M. U1lian have subsequently found that a protein called thrombospondin, 
presumably from the astrocyte, was the chemical messenger that spurred synapse 
building. Thrombospondin plays various biological roles but was not thought to 
be a major factor in the nervous system. The more thrombospondin they added to 
the astrocyte culture, though, the more synapses appeared. Thrombospondin may 
be responsible for bringing together proteins and other compounds needed to 
create a synapse when young nerve networks grow and therefore might contribute 
to the modification of synapses as the networks age.  Future experiments could 
advance our emerging understanding of how glia affect our brains. One 
challenge would be to show that memory--or a cellular analogue of memory, such as 
long-term potentiation--is affected by synaptic astrocytes. Another challenge 
would be to determine precisely how remote synapses might be influenced by signals 
sent through astrocyte circuits.  Perhaps it should not be surprising that 
astrocytes can affect synapse formation at a distance. To form associations 
between stimuli that are processed by different circuits of neurons-the smell of a 
certain perfume, say, and the emotions it stirs about the person who wears 
it--the brain must have ways to establish fast communication between neuronal 
circuits that are not wired together directly, if neurons are like telephones 
communicating electrically through hardwired synaptic connections, astrocytes 
may be like cell phones, communicating with chemical signals that are broadcast 
widely but can be detected only by other astrocytes that have the appropriate 
receptors tuned to receive the message. If signals can travel extensively 
through astrocyte circuits, then glia at one site could activate distant gila to 
coordinate the firing of neural networks across regions of the brain.  
Comparisons of brains reveal that the proportion of glia to neurons increases greatly 
as animals move up the evolutionary ladder. Haydon wonders whether extensive 
connectivity among astrocytes might contribute to a greater capacity for 
learning. He and others are investigating this hypothesis in new experiments. 
Perhaps a higher concentration of glia, or a more potent type of glia, is what 
elevates certain humans to genius. Einstein taught us the value of daring to think 
outside the box. Neuroscientists looking beyond neurons to see how glia may be 
involved in information processing are following that lead. MORE TO EXPLORE  
Driving Mr. Albert: A Trip across America with Einstein's Brain. Michael 
Paterniti. Delta, 2001.  New Insights into Neuron-Glia Communication. R. D. Fields 
and B. Stevens-Graham in Science, Vol. 298, pages 556-562; October 18, 2002.  
Adenosine: A Neuron-Glial Transmitter Promoting Myelination in the CNS in 
Response to Action Potentials. B. Stevens, S. Porta, L. L. Haak, V. Gallo, and R. 
D. Fields in Neuron, Vol. 36, No. 5, pages 855-868; December 5, 2002.  
Astrocytic Connectivity in the Hippocampus. Jai-Yoon Sul, George Orosz, Richard S. 
Givens, and Philip G. Haydon in Neuron Glia Biology, Vol. 1, pages 3-11; 2004.  
Also see the journal Neuron Glia Biology: www.journals.cambridge.org/jid%5fNGB 
Overview/Glia  • For decades, neuroscientists thought neurons did all the 
communicating in the brain and nervous system, and glial cells merely nurtured 
them, even though glia outnumber neurons nine to one.  • Improved imaging and 
listening instruments now show that glia communicate with neurons and with one 
another about messages traveling among neurons. Glia have the power to alter 
those signals at the synaptic gaps between neurons and can even influence where 
synapses are formed.  • Given such prowess, glia may be critical to learning 
and to forming memories, as well as repairing nerve damage. Experiments are 
getting under way to find out.  PHOTO (COLOR): GLIAL CELLS outnumber neurons nine 
to one in the brain and the rest of the nervous system.  PHOTO (COLOR): GLIA 
AND NEURONS work together in the brain and spinal cord. A neuron sends a 
message down a long axon and across a synaptic gap to a dendrite on another neuron. 
Astrocyte gila bring nutrients to neurons as well as surround and regulate 
synapses. Oligodendrocyte gila produce myelin that insulates axons. When a 
neuron's electrical message [action potential] reaches the axon terminal [inset], 
the message induces vesicles to move to the membrane and open, releasing 
neurotransmitters [signaling molecules] that diffuse across a narrow synaptic cleft 
to the dendrite's receptors. Similar principles apply in the body's peripheral 
nervous system, where Schwann cells perform myelination duties.  PHOTO 
(COLOR): ASTROCYTES REGULATE SIGNALING across synapses in various ways. An axon 
transmits a signal to a dendrite by releasing a neurotransmitter (green)--here, 
glutamate. It also releases the chemical ATP [gold]. These compounds then 
trigger an influx of calcium (purple) into astrocytes, which prompts the astrocytes 
to communicate among themselves by releasing their own ATP. Astrocytes may 
strengthen the signaling by secreting the same neurotransmitter, or they may 
weaken the signal by absorbing the neurotransmitter or secreting proteins that 
bind to it (blue), thereby preventing it from reaching its target. Astrocytes can 
also release signaling molecules I red) that cause the axon to increase or 
decrease the amount of neurotransmitter it releases when it fires again. 
Modifying the connections among neurons is one way the brain revises its responses to 
stimuli as it accumulates experience--how it learns. In the peripheral 
nervous system, Schwann cells surround synapses.  PHOTO (COLOR): MOVIE MADE using 
scanning-laser confocal microscopy [later colorized] shows that glial cells 
respond to chattering neurons. Sensory neurons [two large bodies, 20 microns in 
diameter] [al and Schwann glial cells [smaller bodies] were mixed in a lab 
culture containing calcium ions [invisible J. Dye that would fluoresce if calcium 
ions bound to it was introduced into the cells. A slight voltage applied to the 
neurons prompted them to fire action potentials down axons [long lines], and 
the neurons immediately lit up [bl, indicating they had opened channels on 
their membranes to allow calcium to flow inside. Twelve seconds later [c}, as the 
neurons continued to fire, Schwann cells began to light up, indicating they 
had begun taking in calcium in response to the signals traveling down 
axons/Eighteen seconds after that [d], more gila had lit up, because they had sensed 
the signals. The series shows that gila tap into neuronal messages all along the 
lines of communication, not just at synapses where neurotransmitters are 
present.  PHOTO (COLOR): HOW DO GLIA communicate? Gila called astrocytes [a] and 
sensory neurons [not shown] were mixed in a lab culture containing calcium 
ions. After a neuron was stimulated to fire action potentials down long axons 
[lightning bolts] [b], gila began to light up, indicating they sensed the message 
by beginning to absorb calcium. After 10 and 12.5 seconds [c and d], huge 
waves of calcium flux were sweeping across the region, carrying signals among many 
astrocytes. Green to yellow to red depicts higher calcium concentration.  
PHOTO (COLOR)  PHOTO (COLOR)  PHOTO (COLOR)  PHOTO (COLOR)  PHOTO (COLOR)  PHOTO 
(COLOR)  PHOTO (COLOR)  PHOTO (COLOR)  PHOTO (COLOR)  ~~~~~~~~  By R. Douglas 
Fields, R. DOUGLAS FIELDS is chief of the Nervous System Development and 
Plasticity Section at the National Institute of Child Health and Human Development 
and adjunct professor in the Neurosciences and Cognitive Science Program at 
the University of Maryland. He was a postdoctoral fellow at Yale and Stanford 
universities. Fields enjoys rock climbing, scuba diving, and building acoustic 
guitars and Volkswagen engines.  GLIA CONTROL SYNAPSES  FOR YEARS, scientists 
assumed that only neurons specify the connections they make to other neurons. 
But evidence shows that glia can strongly influence how many synapses a neuron 
forms and where it forms them.  Ben A. Barres and his colleagues at Standford 
University found that when they grew neurons form a rat's retina in a lab 
culture devoid of glial cells known as astrocytes, the neurons created very few 
synapses. When the researchers added astrocytes or culture medium that had been 
in contact with astrocytes, synapses formed abundantly. Barres could see the 
synapses and count them through a microscope as well as detect them by r
ecording electrical activity (a sign that signals were flowing through synapses) with 
a microelextrode. He then detected in the medium two chemicals that are 
released by astrocytes to stimulate synapse formation--a fatty complex called 
apoE/cholesterol and the protein thrombospondin.  Meanwhile Jeff W. Lichtman's 
group at Washington University recorded muscle synapses in mice over several days 
or weeks as they formed and as they were removed during development (the time 
when unneeded synapses get pruned) or after injury. When the images were 
spliced into a time-lapse movie, it appeared that both synapse formation and 
elimination were influenced by nonneuronal cells, seen as ghostlike forces acting on 
the axon terminal.  Most recently, Le Tian, Wesley Thompson and their 
associates at the University of Texas at Austin experimented with a mouse that had 
been engineered sot hat its Schwann glia cells fluoresced. This trait allowed 
Thompson's team to collaborate with Lichtman's group and watch glial cells 
operate at the junction where neurons meet muscles--a feat previously not possible. 
After a muscle axon is injured or cut, it withdraws, but a cluster of 
neurotransmitter receptors remains on the recipient side of a synapse. Investigators 
knew that an axon can regenerate and find its way back to the abandoned 
receptors by following the Schwann cells that remain.  But what happens if the axon 
cannot find its way? Tracking the fluorescence, Thompson's group saw that 
Schwann cells at intact synapses somehow sensed that a neighboring synapse was in 
trouble. Mysteriously, the Schwann cells sprouted branches that extended to 
the damaged synapse, forming a bridge along which the axon could grow a new 
projection to the receptors (photographs).  This work clearly shows that glia help 
to determine where synaptic connections form. Researchers are now trying to 
exploit this power to treat spinal cord injuries by transplanting Schwann cells 
into damaged spinal regions in lab animals.  PHOTO (COLOR): GLIA CAN GUIDE 
the formation of synapses. Neurobiologist Le Tian severed a muscle nerve synapse 
in a mouse whose cells had been engineered to fluoresce. Two days later 
Schwann glia cells had formed to bridge across the divide. In another two days, an 
axon had regrown along the bridge to create a synapse. Copyright of Scientific 
American is the property of Scientific American Inc. and its content may not 
be copied or e-mailed to multiple sites or posted to a listserv without the 
copyright holder`s express written permission. However, users may print, 
download, or e-mail articles for individual use. Source: Scientific American, 
Apr2004, Vol. 290 Issue 4, p54, 8p Item: 12462393 Top of Page Formats: 
CitationCitation  HTML Full TextHTML Full Text No previous pages 1 of 1 No additional pages 
Result List | Refine Search PrintPrint  E-mailE-mail  SaveSave Items added to 
the folder may be printed, e-mailed or saved from the View Folder 
screen.Folder is empty.  © 2004 EBSCO Publishing. Privacy Policy - Terms of Use  

----------
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
Visiting Scholar-Graduate Psychology Department, New York University; 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, Human Behavior and Evolution Society, International 
Society for Human Ethology; advisory board member: Youthactivism.org; executive 
editor -- New Paradigm book series.
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
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://lists.extropy.org/pipermail/paleopsych/attachments/20040802/040dee34/attachment.html>