How Do Neurons Communicate?

Author(s): KAREN A. FRENKEL

Source: Scientific American Mind , Vol. 18, No. 6 (December 2007/January 2008), pp. 12-13
Published by: Scientific American, a division of Nature America, Inc.
Stable URL: https://www.jstor.org/stable/10.2307/24939757

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(perspectives)

How Do Neurons Communicate?

The answer is surprisingly elusive—and the subject of intense debate
BY KAREN A. FRENKEL

WE SAY something is “rocket science”

when it is stunningly complex. But
perhaps “neuroscience” would be a
more apt metaphor— the more we
learn about the brain, the more new
questions arise. Case in point is a
seemingly simple question: How do
brain cells communicate? We know
they use chemicals to send messages to
one another. But exactly how do neu-
rons release these neurotransmitters
and then ready themselves to send out
another rapid-fi re message?
This operation takes place on a van-
ishingly small scale— scientists cannot
actually watch the process, so they
have to rely on less direct measures to
determine what is going on. And be-
cause such data can often be interpret-
ed in multiple ways, a controversy
about neurotransmitter release has per-
sisted for decades. Recent advances in
laboratory techniques have escalated
the debate, and the promise of finally
understanding this basic cellular mech-
anism has set the stakes high. The an-
swer is vital because the chemicals in
our brain are implicated in everything
from thought and emotion to mental
illness, addiction and disease.
We already know much about the
journey of a neurotransmitter. Take,
for example, dopamine: Within each
neuron, the chemical is contained in
vesicles, small balloonlike sacs that
transport material throughout the cell.
When a vesicle gets an electrical signal,
it carries the dopamine to the cell wall
Do neurons release their chemical messengers with a brief kiss?
and releases it into the synapse, the
space between neurons. In dopamine’s But what happens to a vesicle after bottles. The fast way is to leave the
case, the signal could be an electrical it dumps its dopamine? This is where bottles intact and simply refi ll them.
S I R I S TA F F O R D G e t t y I m a g e s

impulse generated by your taste buds
after they receive a morsel of choco-
late cake. The signal causes the vesicle
to release its dopamine load, which
floats in the synapse until it is detected
by other neurons that receive the mes-
sage, “This is pleasurable!”
the debate comes in. With a finite
number of vesicles, how do cells rap-
idly respond to subsequent impulses?
Scientists have proposed two main
opposing mechanisms for vesicle re-
cycling, much like the two primary
options available for recycling glass
The slower method involves complete-
ly melting down the bottles and mak-
ing new ones. In cells, the big question
is, Are vesicles ever recycled the fast
way? That is, can they briefly touch
the cell wall, release their contents
and then disengage while retaining

12 SCIENTIFIC AMERICAN MIND D e c e m b e r 2 0 07 /J a nu a r y 2 0 0 8

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 ( “Opponents have moved the goalposts from whether ‘kiss and
run’ exists or not to how prevalent it is,” one expert says. )
their shape? Or are vesicles don’t necessarily imply kiss and
always completely absorbed run.” He cautions against in-
into the cell wall and then re- venting a mechanism to explain
formed later? observations of a very rapid
neuronal response.
Kiss and Run Most researchers, however,
When scientists first began are starting to accept that both
isolating vesicles and studying mechanisms probably exist. “It
them, it was thought that these may be that vesicles undergo
storage containers always com- kiss and run on their way to an
pletely fused with the cell wall, eventual full-collapse event,”
were broken down, and then Tsien says. Ling-Gang Wu of
reassembled later at a kind of the NIH recently measured
cellular bottle factory. In 1961 electrical activity in a brain
researchers found that vesicles center for auditory processing
were coated with a protein. In in rats and found that kiss and
1973 biophysicists John E. run happened in 3 to 17 per-
Heuser, now at Washington cent of recycling events. Kiss-
University School of Medicine, In cells, neurotransmitters are contained within vesi- and-run doubter Ryan points
and Thomas S. Reese of the cles, which appear as small black circles in this elec- out that Wu is the first kiss-
National Institutes of Health tron micrograph. The bottom panel shows vesicles fully and-run proponent who ad-
found this protein to be an es- collapsing into the cell wall as they release their con- mits that it occurs in a minority
sential player in vesicle recon- tents into the surrounding space. of events — an interpretation,
stitution. Two years later the Tsien says, that indicates the
protein was purified and named clath- only a narrow passage opening into debate is no longer about kiss and
rin. Clathrin-aided assembly is now the synapse — it did not appear that the run’s existence. “Opponents have
considered the classical model of vesicle vesicle was in the process of complete- moved the goalposts from whether it
fusion, but it turns out to be rather slow. ly collapsing. Over the years, more so- exists or not to how prevalent it is. We
Researchers can measure how long ves- phisticated experiments have suggest- happily accept their implicit conces-
icle recycling takes by monitoring the ed that kiss and run accounts for at sion and are willing to debate how im-
cell wall’s ability to store electrical least some, if not all, vesicle recycling portant it is,” Tsien says.
charge, or its capacitance. When a ves- events. Many neuroscientists, includ- Although most experts do not feel
icle collapses into the cell wall, the cell’s ing Richard W. Tsien of Stanford Uni- that this debate will be over soon, they
capacitance increases, and when the versity, use fluorescent dye to track the agree on one thing— in the process of
vesicle is reconstituted and breaks away movement of vesicles in single neurons. trying to sort out the details of vesicle
again the capacitance returns to nor- If a vesicle fully collapsed after un- recycling, we are sure to learn a great
mal— and the entire process takes about loading its contents, the dye would be deal about the way neurons work. Pin-
J O H N E . H E U S E R Wa s h i n g t o n U n i v e r s i t y i n S t . L o u i s

30 seconds. expected to dissipate into the synapse. pointing exactly how neurotransmit-
Half a minute seems an eternity in Tsien showed that only some fluores- ters are created and how vesicles trans-
the context of the nervous system, cent markers dispersed, suggesting port and release them could lead the
which must react and respond to doz- that the vesicle remained intact after way to new treatments for depression,
ens of stimuli every second. In 1973 releasing its cargo — consistent with Parkinson’s disease, autism and epi-
biologist Bruno Ceccarelli fi rst pro- the kiss-and-run scenario. lepsy, to name just a few neurotrans-
posed a quick recycling method, But others have found exceptions mission-related disorders. And that
dubbed “kiss and run,” to account for using this and similar dye techniques, kind of knowledge is the real goal. M
fast transmitter release and rapid fi r- and they doubt kiss and run’s ex is-
ing of synapses in frogs. Kiss and run tence. Timothy A. Ryan of Weill Cor- (Further Reading)
also seemed to explain static images nell Medical College thinks the evi-
◆ Curbside Recycling at the Synapse.
captured by electron microscopy that dence is ambiguous at best: “The data Kendall Powell in Journal of Cell Biology,
showed a vesicle at a cell wall with can be interpreted in other ways that Vol. 170, No. 2, page 166; 2005.

w w w. S c i A m M i n d . c o m SCIENTIFIC AMERICAN MIND 13

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