The Other Half of the Brain

8 Pages·2004·0.289 MB·English

by  R. Douglas Fields

The
Other
Half
COPYRIGHT 2004 SCIENTIFIC AMERICAN, INC.
T
he 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 sci-
entists 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
of the
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
Brain 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 sug-
gests 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
MOUNTINGEVIDENCE evaded the immune system. Propped up by glia, neurons were free to
communicate across tiny contact points called synapses and to estab-
SUGGESTSTHAT
lish a web of connections that allow us to think, remember and jump
, for joy.
GLIALCELLS OVERLOOKED
That long-held model of brain function could change dramati-
,
FORHALFACENTURY cally if new findings about glia pan out. In the past several years, sen-
sitive imaging tests have shown that neurons and glia engage in a
MAYBENEARLYAS
two-way dialogue from embryonic development through old age.
Glia influence the formation of synapses and help to determine which
CRITICALTOTHINKING
neural connections get stronger or weaker over time; such changes
ANDLEARNING are essential to learning and to storing long-term memories. And the
most recent work shows that glia also communicate among them-
ASNEURONSARE
selves, in a separate but parallel network to the neural network, in-
fluencing how well the brain performs. Neuroscientists are cautious
about assigning new prominence to glia too quickly, yet they are ex-
cited by the prospect that more than half the brain has gone largely
unexplored and may contain a trove of information about how the
By R. Douglas Fields
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
n
o
ati long, outstretched branch—an axon—that carries electrical signals to
m
ni buds at its end. Each bud emits neurotransmitters—chemical mes-
A
cal senger molecules—across a short synaptic gap to a twiglike receptor,
di
Me or dendrite, on an adjacent neuron. But packed around the neurons
d
bri and axons is a diverse population of glial cells. By the time of Einstein’s
y
HN death, neuroscientists suspected that glial cells might contribute to in-
O
S formation processing, but convincing evidence eluded them. They
N
H
F JO GLIAL CELLS (red) outnumber neurons nine to one eventually demoted glia, and research on these cells slid into the back-
EF in the brain and the rest of the nervous system. water of science for a long time.
J
55
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Astrocyte glia
activate distant
To prove such assertions, scientists first had
neurons to help to show that glia actually do “listen in” on neu-
ronal communication and take action based on
form memories. 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
Neuroscientists failed to detect signaling method called calcium imaging to see whether
among glia, partly because they had insufficient glial cells known as terminal Schwann cells—
analytical technology but primarily because which surround synapses where nerves meet
they were looking in the wrong place. They in- muscle cells—were sensitive to neuronal signals
correctly assumed that if glia could chatter they emitted at these junctions. The method con-
would use the same electrical mode of com- firmed that Schwann cells, at least, did respond
munication seen in neurons. That is, they to synaptic firing and that the reaction involved
would generate electrical impulses called action an influx of calcium ions into the cells.
potentials that would ultimately cause the cells But were glia limited only to eavesdropping
to release neurotransmitters across synapses, on neuronal activity, by scavenging traces of
igniting more impulses in other neurons. In- neurotransmitter leaking from a synapse?
vestigators did discover that glia had many of More general-function Schwann cells also sur-
the same voltage-sensitive ion channels that round axons all along nerves in the body, not
generate electrical signals in axons, but they just at synapses, and oligodendrocyte glia cells
surmised that these channels merely allowed wrap around axons in the central nervous sys-
glia to sense indirectly the level of activity of ad- tem (brain and spinal cord). At my National In-
jacent neurons. They found that glial cells stitutes of Health lab, we wanted to know if
lacked the membrane properties required to ac- glia could monitor neural activity anywhere as
tually propagate their own action potentials. it flowed through axons in neural circuits. If so,
What they missed, and what advanced imaging how was that communication mediated? More
techniques have now revealed, is that glia rely important, how exactly would glia be affected
on chemical signals instead of electrical ones to by what they heard?
convey messages. To find answers, we cultured sensory neu-
Valuable insights into how glia detect neu- rons (dorsal root ganglion, or DRG, cells)
ronal activity emerged by the mid-1990s, after from mice in special lab dishes equipped with
neuroscientists established that glia had a va- electrodes that would enable us to trigger ac-
riety of receptors on their membranes that tion potentials in the axons. We added Schwann
could respond to a range of chemicals, includ- cells to some cultures and oligodendrocytes to
ing, in some cases, neurotransmitters. This dis- others.
covery suggested that glia might communi- We needed to tap independently into the ac-
cate using chemical signals that neurons did tivity of the axons and the glia to determine if
not recognize and at times might react direct- the latter were detecting the axon messages. We
ly to neurotransmitters emitted by neurons. used a calcium-imaging technique to record vi-
sually what the cells were doing, introducing
Overview/Glia
dye that fluoresces if it binds to calcium ions.
When an axon fires, voltage-sensitive ion chan-
■ For decades, neuroscientists thought neurons did all the communicating nels in the neuron’s membrane open, allowing
in the brain and nervous system, and glial cells merely nurtured them, calcium ions to enter. We would therefore ex-
even though glia outnumber neurons nine to one. pect to see the firing as a flash of green fluores-
■ Improved imaging and listening instruments now show that glia cence lighting up the entire neuron from the in-
communicate with neurons and with one another about messages side. As the concentration of calcium rose in a
traveling among neurons. Glia have the power to alter those signals cell, the fluorescence would get brighter. The
at the synaptic gaps between neurons and can even influence where intensity could be measured by a photomulti-
synapses are formed. plier tube, and images of the glowing cells
■ Given such prowess, glia may be critical to learning and to forming could be digitized and displayed in pseudocol-
memories, as well as repairing nerve damage. Experiments are getting or on a monitor in real time—looking some-
under way to find out. thing like the radar images of rainstorms shown
on weather reports. If glial cells heard the neu-
56
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ACTION POTENTIAL
AXON TERMINAL
OLIGODENDROCYTE SYNAPTIC
VESICLE
NEUROTRANSMITTER
SYNAPTIC CLEFT
AXON
RECEPTOR
DENDRITE
SYNAPSE
DENDRITE
ASTROCYTE
BLOOD VESSEL
GLIA AND NEURONS work together in
ronal signals and did so in part by taking up mentally, what exactly had triggered the cal- the brain and spinal cord. A neuron
calcium from their surroundings, they would cium influx? sends a message down a long axon and
across a synaptic gap to a dendrite on
light up as well, only later. Clues came from previous work on other
another neuron. Astrocyte glia bring
Staring at a computer monitor in a dark- glial cells in the brain known as astrocytes. One nutrients to neurons as well as
ened room, my NIHcolleague, biologist Beth of their functions is to carry nutrients from cap- surround and regulate synapses.
Stevens, and I knew that after months of prep- illaries to nerve cells; another is to maintain the Oligodendrocyte glia produce myelin
that insulates axons. When a neuron’s
aration our hypothesis was about to be tested optimal ionic conditions around neurons nec-
electrical message (action potential)
with the flick of a switch. When we turned on essary for firing impulses. Part of the latter job reaches the axon terminal (inset), the
the stimulator, the DRG neurons responded in- is to remove excess neurotransmitters and ions message induces vesicles to move to
stantly, changing from blue to green to red and that neurons release when they fire. In a clas- the membrane and open, releasing
neurotransmitters (signaling
then white on a pseudocolor scale of calcium sic 1990 study, a group led by Stephen J. Smith
molecules) that diffuse across a
concentration, as calcium flooded into the ax- of Yale University (now at Stanford Universi- narrow synaptic cleft to the dendrite’s
ons. Initially, there were no changes in the ty) used calcium imaging to show that the cal- receptors. Similar principles apply in
the body’s peripheral nervous system,
Schwann cells or oligodendrocytes, but about cium concentration in an astrocyte would rise
where Schwann cells perform
15 long seconds later the glia suddenly began suddenly when the neurotransmitter glutamate
myelination duties.
to light up like bulbs on a string of Christmas was added to a cell culture. Calcium waves
lights [see illustration on page 59]. Somehow soon spread throughout all the astrocytes in the
the cells had detected the impulse activity in culture. The astrocytes were responding as if
the axons and responded by raising the con- the neurotransmitter had just been released by
centration of calcium in their own cytoplasm. a neuron, and they were essentially discussing
n
o
ati the news of presumed neuronal firing among
m Glia Communicating with Glia
ni themselves.
A
cal THUS FAR WE HAD confirmed that glia Some neuroscientists wondered whether
di
Me sense axon activity by taking in calcium. In the communication occurred because calcium
d
bri neurons, calcium activates enzymes that pro- ions or related signaling molecules simply
y
HN duce neurotransmitters. Presumably, the in- passed through open doorways connecting
O
S flux in glial cells would also activate enzymes abutting astrocytes. In 1996 S. Ben Kater and
N
H
F JO that would marshal a response. But what re- his colleagues at the University of Utah defused
EF sponse was the cell attempting? More funda- that suspicion. Using a sharp microelectrode,
J
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Schwann glia could
be key to treating
noticing that a familiar molecule kept cropping
nerve diseases up—ATP (adenosine triphosphate), known to
every biology student as the energy source for
such as MS. cellular activities. Although it makes a great
power pack, ATP also has many features that
make it an excellent messenger molecule be-
tween cells. It is highly abundant inside cells but
they cut a straight line through a layer of as- rare outside of them. It is small and therefore
trocytes in culture, forming a cell-free void that diffuses rapidly, and it breaks down quickly.
would act like a highway separating burning All these traits ensure that new messages con-
forests on either side. But when they stimulat- veyed by ATP molecules are not confused with
ed calcium waves on one side of the break, the old messages. Moreover, ATP is neatly pack-
waves spread to astrocytes across the void with aged inside the tips of axons, where neuro-
no difficulty. The astrocytes had to be sending transmitter molecules are stored; it is released
signals through the extracellular medium, together with neurotransmitters at synapses
rather than through physical contact. and can travel outside synapses, too.
ASTROCYTES REGULATE SIGNALING Intensive research in many laboratories In 1999 Peter B. Guthrie and his colleagues
across synapses in various ways.
over the next few years showed similar results. at the University of Utah showed conclusively
An axon transmits a signal to a dendrite
by releasing a neurotransmitter Calcium responses could be induced in astro- that when excited, astrocytes release ATP into
(green)—here, glutamate. It also cytes by adding neurotransmitters or by using their surroundings. The ATP binds to recep-
releases the chemical ATP (gold).
electrodes to stimulate the release of neuro- tors on nearby astrocytes, prompting ion
These compounds then trigger an influx
of calcium (purple) into astrocytes, transmitters from synapses. Meanwhile phys- channels to open and allow an influx of calci-
which prompts the astrocytes to iologists and biochemists were finding that glia um. The rise triggers ATP release from those
communicate among themselves by had receptors for many of the same neuro- cells, setting off a chain reaction of ATP-
releasing their own ATP. Astrocytes
transmitters neurons use for synaptic commu- mediated calcium responses across the popu-
may strengthen the signaling by
secreting the same neurotransmitter, nication, as well as most of the ion channels lation of astrocytes.
or they may weaken the signal by that enable neurons to fire action potentials. A model of how glia around an axon sense
absorbing the neurotransmitter or neuronal activity and then communicate to
secreting proteins that bind to it (blue), ATP Is the Messenger
other glia residing at the axon’s synapse was
thereby preventing it from reaching its
target. Astrocytes can also release THESE AND OTHER RESULTS led to con- coming together. The firing of neurons some-
signaling molecules (red) that cause fusion. Glial communication is controlled by how induces glial cells around an axon to emit
the axon to increase or decrease the calcium influxes, just as neuronal communi- ATP, which causes calcium intake in neigh-
amount of neurotransmitter it releases
cation is. But electrical impulses trigger calci- boring glia, prompting more ATP release,
when it fires again. Modifying the
connections among neurons is one way um changes in neurons, and no such impulse thereby activating communication along a
the brain revises its responses to stimuli exists in or reaches glia. Was glial calcium in- string of glia that can reach far from the initi-
as it accumulates experience—how it
flux initiated by a different electrical phenom- ating neuron. But how could the glia in our ex-
learns. In the peripheral nervous system,
enon or some other mechanism? periment be detecting the neuronal firing, giv-
Schwann cells surround synapses.
In their glial experiments, researchers were en that the axons made no synaptic connec-
tions with the glia and the axonal glia were
CALCIUM nowhere near the synapse? Neurotransmitters
ASTROCYTE AXON TERMINAL were not the answer; they do not diffuse out of
axons (if they did, they could act in unintend-
SIGNALING
ed places in the brain, wreaking havoc). Per-
MOLECULE
haps ATP, which is released along with neuro-
PROTEIN R R. DOUGLAS FIELDS is chief of the Nervous n
THAT BINDS HO System Development and Plasticity Section at atio
NEURO- m
TRANSMITTER AUT tmhaen N Dateivoenlaolp Imnsetnittu aten do fa Cdhjiuldn cHte parltohfe asnsdo Hr uin- cal Ani
HE the Neurosciences and Cognitive Science Pro- d Medi
T gram at the University of Maryland. He was a bri
y
postdoctoral fellow at Yale and Stanford uni- HN
O
GLUTAMATE ATP versities. Fields enjoys rock climbing, scuba HNS
diving, and building acoustic guitars and Volks- F JO
wagen engines. EF
J
GLUTAMATE RECEPTOR
DENDRITE APRIL 2004
COPYRIGHT 2004 SCIENTIFIC AMERICAN, INC.
MOVIE MADE using scanning-laser confocal microscopy
transmitters when axons fire, was somehow es-
(later colorized) shows that glial cells respond to
caping along the axon. chattering neurons. Sensory neurons (two large
To test this notion, we electrically stimulat- bodies, 20 microns in diameter) (a) and Schwann glial
ed pure cultures of DRG axons and then ana- cells (smaller bodies) were mixed in a lab culture
containing calcium ions (invisible). Dye that would
lyzed the medium. By exploiting the enzyme
fluoresce if calcium ions bound to it was introduced
that allows fireflies to glow—a reaction that re- into the cells. A slight voltage applied to the neurons
quires ATP—we were able to detect the release prompted them to fire action potentials down axons
(long lines), and the neurons immediately lit up (b), a
of ATP from axons by seeing the medium glow
indicating they had opened channels on their
when axons fired. We then added Schwann
membranes to allow calcium to flow inside. Twelve
cells to the culture and measured the calcium seconds later (c), as the neurons continued to fire,
responses. They also lit up after axons fired an Schwann cells began to light up, indicating they had
begun taking in calcium in response to the signals
action potential. Yet when we added the en-
traveling down axons. Eighteen seconds after that (d),
zyme apyrase, which rapidly destroys ATP— more glia had lit up, because they had sensed the
thereby intercepting the ATP before it could signals. The series shows that glia tap into neuronal
reach any Schwann cells—the glia remained messages all along the lines of communication, not
just at synapses where neurotransmitters are present.
dark when axons fired. The calcium response
in the Schwann cells had been blocked, because
the cells never received the ATP message. fetus or infant knows which axons will need
ATP released from an axon was indeed trig- myelin and when to start sheathing those ax-
gering calcium influx into Schwann cells. Using ons and, alternatively, how it knows if it should
biochemical analysis and digital microscopy, transform itself into a cell that will not make in- b
we also showed that the influx caused signals sulation. Generally, only large-diameter axons
to travel from the cells’ membrane to the nu- need myelin. Could axon impulses or ATP re-
cleus, where the genes are stored, causing var- lease affect these decisions? We found that
ious genes to switch on. Amazingly, by firing to Schwann cells in culture proliferated more
communicate with other neurons, an axon slowly when gathered around axons that were
could instruct the readout of genes in a glial cell firing than around axons that were quiet.
and thus influence its behavior. Moreover, the Schwann cells’ development was
DS arrested and myelin formation was blocked.
FIEL Axons Control Glia’s Fate Adding ATP produced the same effects.
R. D. TO THIS POINT, work by us and others had Working with Vittorio Gallo and his col-
ND led to the conclusion that a glial cell senses neu- leagues in the adjacent NIHlab, however, we
A
NS ronal action potentials by detecting ATP that found a contrasting situation with the oligo-
E
V
E is either released by a firing axon or leaked dendrocyte glia that form myelin in the brain.
ST
B. from the synapse. The glial cell relays the mes- ATP did not inhibit their proliferation, but c
R
FO sage inside itself via calcium ions. The ions ac- adenosine, the substance left when phosphate
L
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RIVERCH cess that prompts production of the myelin in- Better understanding of myelination is im-
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RTESY OF R. DOUGLAS FIELDS; SOURCE: CIENCE, VOL. 287, PAGES 2267–2271; sfdlgbvroeuireyuocnalr catudedgW tta sii uiis o domaneaenniba lesptl osutyauoaeaur rrifshnoort n snm ocnuheueel.ndoedc srTdn wh. vtu htoe aI a.pati xssism nm i o mit gniynspmr sueshouu,llm ietwlwlnisaapae tdhtbthlsi,ieuo ec a arnceshtencan i cluhdSsael cs iebrkigehoatleh serwsyw ls idy ss ate epa ocnw s wea nttboeurh eadcuuserbe ecl eodclyst loi vc saootuneefnonr---- pabrNtftfirhroneoooooescdnrmm i atps o,au c,r b n anoasofueenoxtuc t . okeron aa Esfnnxted sldvoxso.ee e ewasTnnimrsnmo hys t ms yhe rpwiyee anfloleshteaeirp an,cah ei roatssta ttantttseirhhhrn sxibeakeeogae te fiucpted asotrnsai ldssa oyr atefena n oaxsinldneuusyooes ibnzints .nise doi Mantd fi fa7tte reonu0op isi cnls0re stme gtio rb pipd empymllleeeileenoure leasii dplavcnsdaleleenateiedddees--. d
COUSIN an axon in the peripheral nervous system of a activity in the brain actually influences myeli-
59
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HOW DO GLIA communicate? Glia called astrocytes (a)
in the intricacies of information processing.
and sensory neurons (not shown) were mixed in a lab
culture containing calcium ions. After a neuron was In a footnote to their 1990 paper, Smith
stimulated to fire action potentials down long axons and his colleagues stated that they believed neu-
(lightning bolts) (b), glia began to light up, indicating rons and glia carried on more discrete conver-
they sensed the message by beginning to absorb
sations. Still, the researchers lacked experi-
calcium. After 10 and 12.5 seconds (cand d), huge
waves of calcium flux were sweeping across the region, mental methods precise enough to deliver a
carrying signals among many astrocytes. Green to neurotransmitter in a way that resembled what
a
yellow to red depicts higher calcium concentration.
an astrocyte would realistically experience at
a synapse. In 2003 Philip G. Haydon of the
nation. Such findings could mark paths to treat- University of Pennsylvania achieved this objec-
ment. Drugs resembling adenosine might help. tive. He used improved laser technology to re-
Adding adenosine to stem cells could perhaps lease such a small quantity of glutamate in a
turn them into myelinating glia that are trans- hippocampal brain slice that it would be de-
planted into damaged nerves. tected by only a single astrocyte. Under this
condition, Haydon observed that an astrocyte
Outside the Neuronal Box
sent specific calcium signals to just a small num-
EXPERIMENTS IN OUR LAB and others ber of nearby astrocytes. As Haydon put it, in
strongly suggest that ATP and adenosine me- addition to calcium waves that affect astrocytes
diate the messages coursing through networks globally, “there is short-range connectivity be-
of Schwann and oligodendrocyte glia cells and tween astrocytes.”
b that calcium messages are induced in astrocyte In other words, discrete astrocyte circuits in
glia cells by ATP alone. But do glia have the the brain coordinate activity with neuronal cir-
power to regulate the functioning of neurons, cuits. (The physical or biochemical factors that
other than by producing myelin? define these discrete astrocytic circuits are un-
The answer appears to be “yes.” Richard known at present.) Investigation by others has
Robitaille of the University of Montreal saw also indicated that astrocytes may strengthen M
A
the voltage produced by synapses on frog mus- signaling at synapses by secreting the same neu- AH
R
G
cle become stronger or weaker depending on rotransmitter the axon is releasing—in effect, S-
N
E
what chemicals he injected into Schwann cells amplifying the signal. V
E
at the synapse. When Eric A. Newman of the The working hypothesis that Haydon and B. ST
University of Minnesota touched the retina of I, along with our colleagues, are reaching from ND
A
a rat, waves of calcium sent by glia changed the these discoveries is that communication among DS
L
E
visual neurons’ rate of firing. Studying slices of astrocytes helps to activate neurons whose ax- FI
D.
rat brain taken from the hippocampus—a re- ons terminate relatively far away and that this R.
c gion involved in memory—Maiken Neder- activity, in turn, contributes to the release of FOR
L
gaard of New York Medical College observed neurotransmitters at distant synapses. This ac- RIA
synapses increase their electrical activity when tion would regulate how susceptible remote ATEON
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OP
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R2
sis of learning. role of glia to include participation in the for- VED FR 18,
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are necessary if glial cells are to be involved called thrombospondin, presumably from the COUSIN
60
SCIENTIFIC AMERICAN APRIL 2004
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GLIA CONTROL SYNAPSES
astrocyte, was the chemical messenger that
FOR YEARS, scientists assumed that only neurons
spurred synapse building. Thrombospondin
specify the connections they make to other neurons.
plays various biological roles but was not
But evidence shows that glia can strongly influence
thought to be a major factor in the nervous sys-
how many synapses a neuron forms and where it
tem. The more thrombospondin they added to forms them.
the astrocyte culture, though, the more synaps- Ben A. Barres and his colleagues at Stanford
es appeared. Thrombospondin may be respon- University found that when they grew neurons from a
sible for bringing together proteins and other rat’s retina in a lab culture devoid of glial cells known
compounds needed to create a synapse when as astrocytes, the neurons created very few
young nerve networks grow and therefore synapses. When the researchers added astrocytes or
culture medium that had been in contact with
might contribute to the modification of synaps-
astrocytes, synapses formed abundantly. Barres
es as the networks age.
could see the synapses and count them through a
Future experiments could advance our
microscope as well as detect them by recording
emerging understanding of how glia affect our
electrical activity (a sign that signals were flowing
brains. One challenge would be to show that
through synapses) with a microelectrode. He then
memory—or a cellular analogue of memory, detected in the medium two chemicals that are
such as long-term potentiation—is affected by released by astrocytes to stimulate synapse
GLIA CAN GUIDE the formation
synaptic astrocytes. Another challenge would formation—a fatty complex called apoE/cholesterol of synapses. Neurobiologist
be to determine precisely how remote synaps- and the protein thrombospondin. Le Tian severed a muscle nerve
es might be influenced by signals sent through Meanwhile Jeff W. Lichtman’s group at Washington synapse in a mouse whose
astrocyte circuits. University recorded muscle synapses in mice over cells had been engineered to
fluoresce. Two days later (top)
several days or weeks as they formed and as they
Perhaps it should not be surprising that as- Schwann glia cells (dark red)
were removed during development (the time when
trocytes can affect synapse formation at a dis- had formed a bridge across the
tance. To form associations between stimuli unneeded synapses get pruned) or after injury. When divide (arrow). In another two
the images were spliced into a time-lapse movie, it days (bottom), an axon
that are processed by different circuits of neu-
appeared that both synapse formation and (green) had regrown along the
rons—the smell of a certain perfume, say, and elimination were influenced by nonneuronal cells, bridge to create a synapse.
the emotions it stirs about the person who
seen as ghostlike forces acting on the axon terminal.
wears it—the brain must have ways to establish Most recently, Le Tian, Wesley Thompson and their associates at the
fast communication between neuronal circuits University of Texas at Austin experimented with a mouse that had been
that are not wired together directly. If neurons engineered so that its Schwann glia cells fluoresced. This trait allowed
are like telephones communicating electrically Thompson’s team to collaborate with Lichtman’s group and watch glial cells
through hardwired synaptic connections, as- operate at the junction where neurons meet muscle—a feat previously not
trocytes may be like cell phones, communicat- 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.
ing with chemical signals that are broadcast
Investigators knew that an axon can regenerate and find its way back to the
widely but can be detected only by other astro-
abandoned receptors by following the Schwann cells that remain.
cytes that have the appropriate receptors tuned
But what happens if the axon cannot find its way? Tracking the fluorescence,
to receive the message. If signals can travel ex-
Thompson’s group saw that Schwann cells at intact synapses somehow sensed
tensively through astrocyte circuits, then glia at
that a neighboring synapse was in trouble. Mysteriously, the Schwann cells
one site could activate distant glia to coordinate sprouted branches that extended to the damaged synapse, forming a bridge along
the firing of neural networks across regions of which the axon could grow a new projection to the receptors (photographs).
the brain. This work clearly shows that glia help to determine where synaptic
Comparisons of brains reveal that the pro- connections form. Researchers are now trying to exploit this power to treat
portion of glia to neurons increases greatly as spinal cord injuries by transplanting Schwann cells into damaged spinal
animals move up the evolutionary ladder. Hay- regions in lab animals. —R.D.F.
don wonders whether extensive connectivity
among astrocytes might contribute to a greater
MORE TO EXPLORE
capacity for learning. He and others are inves-
tigating this hypothesis in new experiments. Driving Mr. Albert: A Trip across America with Einstein’s Brain. Michael Paterniti. Delta, 2001.
N
SO Perhaps a higher concentration of glia, or a New Insights into Neuron-Glia Communication. R. D. Fields and B. Stevens-Graham in
P
OM more potent type of glia, is what elevates cer- Science, Vol. 298, pages 556–562; October 18, 2002.
H
Y T tain humans to genius. Einstein taught us the Adenosine: A Neuron-Glial Transmitter Promoting Myelination in the CNS in Response to
LE Action Potentials. B. Stevens, S. Porta, L. L. Haak, V. Gallo, and R. D. Fields in Neuron, Vol. 36,
WES value of daring to think outside the box. Neu- No. 5, pages 855–868; December 5, 2002.
D roscientists looking beyond neurons to see how
AN Astrocytic Connectivity in the Hippocampus. Jai-Yoon Sul, George Orosz, Richard S. Givens,
AN glia may be involved in information processing and Philip G. Haydon in Neuron Glia Biology, Vol. 1, pages 3–11; 2004.
LE TI are following that lead. Also see the journal Neuron Glia Biology: www.journals.cambridge.org/jid–NGB
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