Eye, Brain, and Vision

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 be-
comes 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 trans-
fer 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 scis-
sors 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 second.
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 millivolts,
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 inten-
sity 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 impor-
tant, and the nervous system has evolved a special mechanism for increasing it.
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 sections.
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.

                           SYNAPTIC TRANSMISSION
    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 re-
markable machine. First, it contains special channels that respond to depolar-
ization 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 under-
stood, this arrival of calcium inside the cell leads to the expulsion, across the
membrane from inside to outside, of packages of special chemicals call neuro-
transmitters. 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 gener-
ally 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 pro-
tein 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 neu-
rotransmitter is released and which receptor molecules are present. Acetylcho-
line, the best-known transmitter, is in some synapses excitatory and in others
inhibitory: it excites limb and trunk muscles but inhibits the heart. Noradrena-
line is usually excitatory; gamma-amino butyric acid (GABA) is usually inhib-
itory. As far as we know, a given synapse remains either excitatory or inhibi-
tory for the life of the animal.
Any one nerve cell is contacted along its dendrites and cell body by tens,
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 to-
gether. 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 nerve cells,
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 impulses,
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 depo-
larization of a given size is most likely to produce a regenerative impulse,
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, depolar-
ization 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 stimu-
lus 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 essentially
analog.