can flow out to compensate and quickly restore the membrane to its
resting state. But suppose that the initial charge transfer is so large, and
so many sodium pores open, that more charge is brought in by sodium than can
be removed by potassium: the membrane will then depolarize still further.
This will cause even more sodium pores to open, and still more depolarization,
and so on, in a regenerative, explosive process. When all the sodium pores
have opened that can open, the membrane potential is reversed in sign, relative
to the resting potential: instead of being 70 millivolts, positive outside,
it becomes 40 millivolts, negative outside.
The reduction in potential across the membrane, with ultimate reversal
of potential, doesn't take place all at once along the fiber's length,
because transfer of charge requires time. It starts in one place and spreads along
the fiber at a rate of.0.1 to 10 or so meters per second. At any instant there will
be one active region of charge reversal, perhaps several inches long, and this
reversal will be traveling away from the cell body, with still unopened channels
ahead of it and reclosed channels, temporarily incapable of reopening, behind.
This event constitutes the impulse. You can see that the impulse is
not at all like the current in a copper wire. No electricity or ions or anything
tangible travels along the nerve, just as nothing travels from handle to point
when a pair of scissors closes. (Ions do flow in and out, just as the blades
of the scissors move up and down.) It is the event, the intersection of the blades of
the scissors or the impulse in the nerve, that travels.
Because it takes some time before sodium channels are ready for another opening and closing, the highest rate at which a cell or axon can fire
impulses is about 800 per second. Such high rates are unusual, and the rate of firing
of a very active nerve fiber is usually more like 100 or 200 impulses per
One important feature of a nerve impulse is its all-or-none quality.
If the original depolarization is sufficient—if it exceeds some threshold
value, (going from the resting level of 70 millivolts to 40 millivolts, positive outside)—the process becomes regenerative, and reversal occurs all the way to 40
negative outside. The magnitude of the reversed potential traveling
down the nerve (that is, the impulse) is determined by the nerve itself, not
by the intensity of the depolarization that originally sets it going. It is analogous
to any explosive event. How fast the bullet travels has nothing to do with
how hard you pull the trigger.
For many brain functions the speed of the impulse seems to be very important, and the nervous system has evolved a special mechanism for increasing
Glial cells wrap their plasma membrane around and around the axon like
a jelly roll, forming a sheath that greatly increases the effective thickness
of the nerve membrane. This added thickness reduces the membrane's capacitance, and hence the amount of charge required to depolarize the nerve. The layered substance, rich in fatty material, is called myelin. The sheath is interrupted every few millimeters, at nodes ofRanvier, to allow the currents associated
with the impulse to enter or leave the axon. The result is that the nerve
impulse in effect jumps from one node to the next rather than traveling continuously along the membrane, which produces a great increase in conduction velocity.
The fibers making up most of the large, prominent cables in the brain
are myelinated, giving them a glistening white appearance on freshly cut
White matter in the brain and spinal cord consists of myelinated axons
but no nerve cell bodies, dendrites, or synapses. Grey matter is made up mainly
of cell bodies, dendrites, axon terminals, and synapses, but may contain myelinated axons.
The main gaps remaining in our understanding of the impulse, and also
the main areas of present-day research on the subject, have to do with the
structure and function of the protein channels.
How are impulses started up in the first place, and
what happens at the far end, when an impulse reaches the end of an axon?
The part of the cell membrane at the terminal of
an axon, which forms the first half of the synapse (the presynaptic membrane), is a specialized
and remarkable machine. First, it contains special channels that respond to
depolarization by opening and letting positively charged calcium ions through.
Since the concentration of calcium (like that of sodium) is higher outside
the cell than inside, opening the gates lets calcium flow in. In some way still not
understood, this arrival of calcium inside the cell leads to the expulsion,
across the membrane from inside to outside, of packages of special chemicals call
neurotransmitters. About twenty transmitter chemicals have been identified,
and to judge from the rate of new discoveries the total number may exceed fifty.
Transmitter molecules are much smaller than protein molecules but are
generally larger than sodium or calcium ions. Acetylcholine and noradrenaline
are examples of neurotransmitters. When these molecules are released from
the presynaptic terminal they quickly diffuse across the 0.02-micrometer
synaptic gap to the postsynaptic membrane.
The postsynaptic membrane is likewise specialized: embedded in it are
protein pores called receptors, which respond to the neurotransmitter by
causing channels to open, allowing one or more species of ions to pass through.
Just which ions (sodium, potassium, chloride) are allowed to pass determines whether the postsynaptic cell is itself depolarized or is stabilized
and prevented from depolarizing.
To sum up so far, a nerve impulse arrives at the axon terminal and causes special neurotransmitter molecules to be released. These neurotransmitters
act on the postsynaptic membrane either to lower its membrane potential
or to keep its membrane potential from being lowered. If the membrane potential
is lowered, the frequency of firing increases; we call such a synapse excitatory.
If instead the membrane is stabilized at a value above threshold, impulses
do not occur or occur less often; in this case, the synapse is termed inhibitory.
Whether a given synapse is excitatory or inhibitory depends on which
neurotransmitter is released and which receptor molecules are present.
Acetylcholine, the best-known transmitter, is in some synapses excitatory and
in others inhibitory: it excites limb and trunk muscles but inhibits the heart.
Noradrenaline is usually excitatory; gamma-amino butyric acid (GABA) is usually
inhibitory. As far as we know, a given synapse remains either excitatory
or inhibitory for the life of the animal.
Any one nerve cell is contacted along its dendrites and cell body by
hundreds, or thousands of terminals; at any instant it is thus being
told by some synapses to depolarize and by others not to. An impulse coming
in over an excitatory terminal will depolarize the postsynaptic cell; if an
impulse comes in simultaneously over an inhibitory terminal, the effects of
the two will tend to cancel each other. At any given time the level of the membrane potential is the result of all the excitatory and inhibitory influences
added together. A single impulse coming into one axon terminal generally has
only a miniscule effect on the next cell, and the effect lasts only a few milliseconds before it dies out. When impulses arrive at a cell from several other
the nerve cell sums up, or integrates, their effects. If the membrane
potential is sufficiently reduced—if the excitatory events occur in enough
terminals and at a high enough rate—the depolarization will be enough to generate
usually in the form of a repetitive train. The site of impulse initiation
is usually where the axon leaves the cell body, because this happens to be where
a depolarization of a given size is most likely to produce a regenerative
perhaps owing to an especially high concentration of sodium channels
in the membrane. The more the membrane is depolarized at this point, the greater the number of impulses initiated every second.
Almost all cells in the nervous system receive inputs from more than
one other cell. This is called convergence. Almost all cells have axons
that split many times and supply a large number of other nerve cells—perhaps hundreds
or thousands. We call this divergence. You can easily see that without
convergence and divergence the nervous system would not be worth much: an excitatory synapse that slavishly passed every impulse along to the next cell would
serve no function, and an inhibitory synapse that provided the only input
to a cell would have nothing to inhibit, unless the postsynaptic cell had some
special mechanism to cause it to fire spontaneously.
I should make a final comment about the signals that nerve fibers transmit.
Although most axons carry all-or-none impulses, some exceptions exist.
If local depolarization of a nerve is subthreshold—that is, if it
is insufficient to start up an explosive, all-or-none propagated impulse—it will
nevertheless tend to spread along the fiber, declining with time and with distance
from the place where it began. (In a propagated nerve impulse, this local spread
is what brings the potential in the next, resting section of nerve membrane
to the threshold level of depolarization, at which regeneration occurs.) Some
axons are so short that no propagated impulse is needed; by passive spread,
depolarization at the cell body or dendrites can produce enough depolarization
at the synaptic terminals to cause a release of transmitter. In mammals, the
cases in which information is known to be transmitted without impulses are few
but important. In our retinas, two or three of the five nerve-cell types
function without impulses.
An important way in which these passively conducted signals differ from impulses—besides their small and progressively diminishing amplitude—is that their size varies depending on the strength of the stimulus. They
are therefore often referred to as graded signals. The bigger the signal,
the more depolarization at the terminals, and the more transmitter released.
You will remember that impulses, on the contrary, do not increase in size as
the stimulus increases; instead, their repetition rate increases. And the faster
an impulse fires, the more transmitter is released at the terminals. So the final
result is not very different. It is popular to say that graded potentials represent
an example of analog signals, and that impulse conduction, being all or none, is
digital. I find this misleading, because the exact position of each impulse in
a train is not in most cases of any significance. What matters is the average rate
in a given time interval, not the fine details. Both kinds of signals are thus