THE STRUCTURE OF A NEURON

Long after biologists had agreed cells make up all other organs and tissues, neuroscientists
continued to debate that essential truth for the nervous system. The two recipients of the Nobel
Prize for Physiology or Medicine in 1906 were on opposite sides of the argument. C. Golgi
thought the nervous system was a reticulum whereas S. Ramon y Cajal concluded the brain and
spinal cord consisted of individual cells. The term, neuron, was applied to the cells responsible
for most neural functions whereas glia (literally, glue) was the term used for supporting cells in
the nervous system. By the turn of the 20th century neuroscientists were persuaded by Cajals
data and arguments to accept the neuron doctrine over Golgis reticular theory. But some 90
billion neurons and an equal number of glia populate the human brain and spinal cord and they
are richly interconnected to form large functional units. That leads us to ponder what we need to
know about an individual neuron to make sense of nervous system organization and function.
For a fundamental understanding of a single neuron we can divide what is known into two
groups of data:
1) Neurons have a complex shape and are organized in a way that can be described as dynamic
polarization (Figure 1). Neurons have many processes. For each neuron, processes called
dendrites are most active in the reception of information from other neurons whereas a single,
long process called an axon is responsible for conduction and transmission of information to
other neurons.
2) To achieve these basic functions of reception and transmission, neurons establish and maintain
complex shapes and they form elaborate contacts with other cells.
DYNAMIC POLARIZATION
Let us parse the term, dynamic polarization. The term polarity is used to describe many types of
cells in which one region performs one function while a second region does something else. For
some cells, such as those of the kidney, polarity is a matter of moving water or some aqueous
compound from one end to the other; absorption occurs at one end and release at the other end.
But for neurons, polarity exists to move information. A neuron receives information at one
pole and transmits it at the other pole. That, at least, is the case for 95% of neurons, 95% of the
time. We will encounter exceptions throughout the nervous system, but as a first step toward a
mature understanding of a neuron it is fair to say reception and transmission of information occur
at different ends of most neurons. All of this is dynamic because the strength and content of
input and output varies from one moment to the next. Because a single neuron typically
receives information from several hundred other neuron and gives off information to several
hundred more there is a great deal of room to change how any neuron responds to

ELECTRICAL

CHEMICAL

Fig 1. Dynamic polarization is an effective simplification. It says a neuron receives information

at one end or pole, integrates it and then sends it to targets at the other end. The two poles do
different things. The light microscopic appearance of a neuron accents the presence of distinct
surfaces along a neuron. They include surfaces that function to receive signals from other
neurons (cell body and dendrites), a surface in which all signals are integrated (axon hillock and
initial segment) and surfaces along which the integrated signal is conducted (axon) and then
transmit to other neurons (axon terminals). This separation of function...the presence of
different parts of the neuron performing different functions... is dynamic polarization. Events
within a neuron the reception, integration and conduction of information are electrical in
nature. They involve changes in voltage produced by the flow of current. Events between
neurons are chemical transmission from one neuron to another requires the release of
chemical messengers called neurotransmitters.
FOUR AQUEOUS IONS ARE UNEVENLY DISTRIBUTED ACROSS THE PLASMA MEMBRANES OF
NEURONS. The cell membrane of a neuron separates intracellular fluid from extracellular fluid.
The two fluids have very different concentrations of ions, with four aqueous ions being of
particular importance. They are the cations, Na+, K+, Ca2+ and the anion, Cl- (Figure 2). A fifth
sort of ion referred to as organic anions (negatively charged proteins) are also present in the two
fluids and are at much greater concentration inside a neuron. Two sorts of proteins in the plasma
membrane called pumps (primary exchangers) and secondary exchangers consume energy to
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move ions from a place of lesser concentration to a place of greater concentration. These pumps
and secondary exchangers are responsible for setting up and maintaining the uneven distribution
of ions on the two sides of the plasma membrane.
LEAKAGE OF K+ ACROSS THE PLASMA MEMBRANE PRODUCES A VOLTAGE DIFFERENCE
BETWEEN CYTOSOL AND EXTRACELLULAR FLUID. The law of electroneutrality states that in a
biological system every anion (negative charge) has an accompanying cation (positive charge).
Pumps and secondary exchangers do not change that rule, but channels can. A channel is a
simple hole in the membrane that allows an ion to move passively, most often from a place of
greater concentration to a place of lower concentration. This is simply thermodynamics as in
forcing air into a balloon and then letting go of it. Air moves to become equally concentrated
inside and outside the balloon. Ions will do the same if they given the chance, and channels open
to give them the chance. Channels are composed of transmembrane proteins that line up to form
a tiny hole through which ions can flow. The uneven distribution of K+ and its selective
leakage across the membrane produces a voltage difference across the membrane this is
called the membrane potential. For most neurons the membrane potential is around -70 mV,
which means intracellular fluid is 70 mV more negative than extracellular fluid.
Fig 2. Na+, K+, Ca2+ and Cl- are unevenly distributed
across the cell membrane. Of most immediate concern
are the concentrations of K+ and Na+ the much higher
concentration of K+ on the inside and the much higher
concentration of Na+ on the outside. Several types of
channels exist that permit ions to pass through the
membrane from region of higher concentration to
region of lower concentration. One has no gate it is
always open and allows K+ to leak across the membrane
from inside to outside. This leak channel permits
positive charge to move from the inside a neuron
(cytosol) to outside (extracellular fluid); and that
movement leaves behind a net negative charge. Other
channels are gated, usually by voltage or the presence
of a chemical messenger (also called a ligand). These
channels stay closed unless the membrane potential
changes or a ligand binds to a receptor protein. Ions
also move from regions of lower concentration to
regions of higher concentration to maintain the
imbalance seen in this figure, but that movement
requires the consumption of energy (such as ATP) by
primary and secondary exchangers.
RESTING MEMBRANE POTENTIAL IS THE PRODUCT OF K+ FLOW THROUGH LEAK CHANNELS. A
neuron has a membrane potential of something close to -70 mV because even when the neuron is
at rest, a type of channel called a leak channel is open; this leak channel permits of K+ to move
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from the cytosol, where it exists at a concentration of 135-140 mM, to extracellular fluid, where
the concentration is only 3-5 mM). As K+ moves outward through these leak channels driven
outward by the difference in its concentration between cytosol and extracellular fluid it leaves
behind negative charge in the cytosol and adds more positive charge to extracellular fluid. That
production of negative charge in the cytosol and addition of positive charge to extracellular
fluid generates a voltage gradient; this is a difference in voltage between inside and outside
a neuron. The charge builds up and would continue to build up until the electrical force of the
voltage difference between inside and outside is exactly equal and opposite to the
thermodynamic force in the concentration difference between inside and outside. Think of this
way: the thermodynamic force is pushing K+ outward but the electrical force generated by excess
negative charge inside the cell is inviting K+ to stay in the cytosol. So far as K+ in the cytosol is
concerned, the thermodynamic force is repulsive whereas the electrical force is attractive. At the
voltage where the attractive electrical force is equal to the repulsive thermodynamic (chemical)
forces, no net flow of K+ occurs. For every K+ that moves out of the cell, one moves back in.
This voltage at which no net flow of K+ occurs is called the equilibrium potential for K+.
Fig 3. If Na+ is allowed to enter the
cell, a depolarization occurs. This
moves the membrane potential
away from -70 mV to a less
negative state (for example -60
mV). The depolarization at a
synapse is called an excitatory
postsynaptic potential (EPSP).

NEURONS USE THE MEMBRANE POTENTIAL FOR COMMUNICATION. A few hundred million
neurons act as sensory receptors; they are sensitive to the energy in a sensory stimulus, such as
photons or heat or mechanical energy. Information reaching all other neurons comes to them
by way of contacts with other neurons. These contacts are called synapses. Many synapses
work by opening ions channels in the plasma membrane, thereby making the membrane more
permeable to one ion or a few ions. That change in ion permeability produces a change in
membrane potential. What matters for any one synapse, then, is which ions are allowed to enter
or leave the postsynaptic cell (Figures 3 and 4). If one set of channels opens and cations enter
the cytosol from extracellular fluid (Na+ in particular) the result is movement of the membrane
potential from -70 mV to some, more positive value such as to -69 mV or to -65 mV or to some
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other value that is determined by how many ion channels open and how well each channel allows
ions to move through them. But if a different set of ion channels opens and Cl- is allowed to
enter the cytosol from extracellular fluid, the result is movement of the membrane potential to a
more negative value. The membrane potential goes from -70 mV to -71 mV, for example. The
term depolarization is used to describe movement of the membrane potential from one level to a
more positive value; hyperpolarization is movement to a more negative value. For reasons that
will become clearer very shortly, depolarization produced at a synapse is called an excitatory
postsynaptic potential (EPSP) whereas hyperpolarization produced at a synapse is called
an inhibitory postsynaptic potential (IPSP).
Together, Figures 3 and 4 make an essential point when it comes to the structure of a neuron.
When we speak of receptive surfaces for a neuron we most often mean surfaces that receive
synaptic contacts from other neurons. And when we speak of transmitting surfaces of a
neuron we are talking about places where that neuron forms synapses with other neurons. The
purposes of the receptive, integrating and conducting surfaces of a neuron are to take synapses
from other neurons often hundreds of other neurons figure out what they mean and carry that
information to other neurons by way of its own synapses.
Fig 4. Other synapses permit Cl- to enter
a cell. This drives the membrane
potential to a more negative state (from 70 mV to -75 mV) called a
hyperpolarization. We often called
hyperpolarizations inhibitory postsynaptic
potentials (IPSPs).

AN ELECTROCHEMICAL GRADIENT IS THE FORCE THAT MOVES AN ION FROM ONE SIDE OF THE
PLASMA MEMBRANE TO THE OTHER. Chemical gradients are the uneven distribution of ions
produced by pumps and exchangers; as K+ or any other ion is allowed to move across the plasma
membrane, down its concentration gradient (from higher concentration to lower), it produces an
electrical gradient. That is the result of moving charge from one side of the plasma membrane to
the other; excess positive charge accumulates on one side and excess negative charge
accumulates on the other. The combination of electrical and chemical forces on the movement
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of an ion is referred to as the electrochemical gradient. Notice that for K+ the two forces work
against one another (Figure 5). The chemical gradient for K+ is strongly outward whereas the
electrical gradient is strongly inward. Were the resting membrane potential to reach -102 mV,
the inward electrical gradient would be so strong as to precisely counterbalance the outward
chemical gradient. At -102 mV, then, no net flow of K+ would occur across the plasma
membrane; this is the equilibrium potential for K+. But at -70 mV, the combined
electrochemical gradient for K+ is weakly outward. For Na+ the two forces work together when
a neuron is at rest. A ten-fold greater concentration of Na+ in extracellular fluid and a membrane
potential of -70 mV add together to produce a strong electrochemical gradient that drives Na+
into the cytosol whenever Na+ channels open in the plasma membrane.
Fig 5. As shown in Figure 2, K+ exists at a concentration inside a neuron
30 times greater than the concentration outside. By contrast, Na+ is 10
times more concentrated outside than in. Thus, each ion has a
concentration gradient - a steep chemical hill - that drives the
movement of the ion across the membrane, from region of higher
concentration to region of lower concentration. This is a simple matter
of thermodynamics the drive to produce a random distribution means
ions will flow down a concentration gradient unless they are either
prevented from doing so by some barrier or are opposed by some other
force. The flow of ions, particularly K+, produces a voltage gradient.
Negative charge builds up inside a neuron as K+ leaks outward. That
intracellular negative charge is a gradient that influences the flow of
ions across the membrane. Voltage and chemical gradients can either
work together to drive an ion across the membrane or they can work in
opposing directions, one to drive an ion across the membrane and the
other to keep it in place.

CHANNELS ARE COMPOSED OF TRANSMEMBRANE PROTEINS THAT OPEN TO PERMIT IONS TO

FLOW ACROSS THE MEMBRANE. Channels allow ions to move down their electrochemical
gradients, which usually means an ion moves from a region of higher concentration to a region
of lower concentration. Thus channels require no energy to move ions; all they need do is open.
Channels come in a variety of types, most of which are closed when the membrane potential is at
resting levels. Those channels have molecular gates that are usually closed they prevent ions
from moving through the channel but those channels can be instructed to spring open under
appropriate circumstances. For the great majority of channels in the plasma membrane of a
neuron, one of two things causes a particular gate to open; those are either the binding of a
signaling molecule (a ligand) or a change in membrane potential. Each of them requires some
explanation.
BINDING OF A SIGNALING MOLECULE CAN LEAD TO OPENING OF ION CHANNELS. Some
channels are ligand-gated ion channels. These channels are transmembrane proteins that bind
specific molecules on either the outer surface of the plasma membrane or on its inner surface; in
binding these molecules, the channel protein changes shape briefly and it opens to allow ions to
flow from one side of the membrane to the other. Ligand means nothing more than a molecule
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that binds specifically to a receptor protein and produces a specific action. Many ligand-gated
channels in the nervous system are neurotransmitter receptors they bind molecules released
by one neuron to affect an adjacent neuron but other ligand-gated ion channels open when
they bind molecules made or released inside a neuron (that is, they are receptors for intracellular
ligands). All ligand-gated ion channels are absolutely selective for the flow of cations
(positively charged ions) versus anions (negatively charged ions). And so a specific channel will
allow either Na+ and Ca2+ and K+ to move across the plasma membrane or it will allow Cl- to do
likewise. No channel opens to allow both cations and anions to move through it. Many cation
channels are non-specific and will allow all three of the major cations to move across the plasma
membrane but other channels are selective for the flow of one cation (for example, they allow
only Na+ to move through them). Ligand-gated ion channels are the principal means by which
one neuron receives the information transmitted by other neurons. And so all along the
receptive surfaces of a neuron is a wealth of ligand-gated ion channels.
CHANGES IN MEMBRANE POTENTIAL (VOLTAGE) LEADS TO THE OPENING OF SOME ION
CHANNELS. The gates of some channels open or close when the voltage of the membrane
changes, usually when the membrane potential becomes more positive (e.g. goes from -70 mV to
-50 mV). As a class, channels that open in response to changes in membrane voltage are called
voltage-gated channels. The most important types of voltage-gated channels allow cations to
enter or leave the cytosol of a neuron and in most cases, these voltage-gated channels are
selective for only one cation. They allow Na+ to enter a cell, or Ca2+ to enter a cell or K+ to leave
a cell.
LIGAND-GATED Na+ CHANNELS AND VOLTAGE-GATED Na+ CHANNELS ARE RESPONSIBLE FOR
+
VERY DIFFERENT TYPES OF DEPOLARIZING EVENTS. Ligand-gated Na channels are by far the
most common means by which depolarizing synaptic potentials or EPSPs are generated in
neurons of the central nervous system (Figure 4). Binding of neurotransmitter molecules to this
type of channel produces a brief period of Na+ influx into a cell; the influx leads to a small
depolarization, typically in the range of 1 mV. Opening of voltage-gated Na+ channels, by
contrast, produces a very different type of membrane potential called an action potential
(Figure 6). Whereas synaptic potentials are local and graded changes in membrane voltage,
action potentials are all-or-none, complete reversals in membrane potential, in which the voltage
of a neuron goes from -50 mV to +40 mV in 1 millisecond. Rather than local changes in
membrane potential, action potentials invade all parts of a neuron. They begin in the first part of
an axon, referred to as its initial segment, but they actively propagate into all parts of a neuron
and remain equally strong throughout a neurons length. Action potentials are the critical
mechanism used by most neurons to take what they receive and turn it into something they
transmit.

Fig 6.
Electrical
potentials
recorded from
an electrode
vary with the
location of the
electrode and
with synaptic
activity in a
neuron watch
as we go from left to right in this record. The electrical potential recorded from an electrode as
it goes from extracellular fluid into a neuron drops from 0 mV (because we use extracellular
fluid as a reference point or ground) to -65 mV this is the resting membrane potential of a
neuron. The first three potentials recorded from inside the neuron are referred to as passive
responses these are synaptic potentials. Two of them are hyperpolarizations or IPSPs that
make the neuron more negative. The third is a weak depolarization or EPSP. It raises the
membrane potential to -60 mV but it dies off with time and distance. Soon the membrane
potential is back to -65 mV. The next depolarization and several thereafter carry the membrane
potential to -55mV. This is the threshold for initiation of an action potential and what happens
as a result is a very brief (1 millisecond) reversal in membrane potential. It peaks at +40 mV
and returns very quickly to -65 mV. You would see the same reversal in membrane potential
with its full height no matter where you recorded from a neuron after an action has been
initiated. Action potentials are all or none they are digital signals that vary in frequency but
never in size.
With these principles in mind - that neurons use ions to carry information from one neuron to the
next and from one part of a neuron to all other parts of that same neuron let us return to looking
at the structure behind the dynamic polarization of a neuron.

RECEPTIVE SURFACES OF A NEURON INCLUDE THE CELL BODY AND DENDRITES.

EVERY NEURON HAS A CELL BODY OR SOMA. The importance of the soma for neuronal
communication lies in two features. In the first place, the soma gives off all the neurons
processes. Those processes include the dendrites, which make up the majority of the receptive
surface of a neuron, and the axon, the one process that is the conducting/transmitting element of
a neuron (Figure 7). And for most neurons the cell body is, itself, a receptive surface it
receives synapses. Depending on the part of the CNS we examine and the type of neuron we
examine, some cell bodies receive both excitatory and inhibitory synapses whereas other cell
bodies receive only inhibitory synapses.
DENDRITES ARE RECEPTIVE EXTENSIONS OF THE CELL BODY. Cell bodies of neurons typically
give rise to several processes called dendrites, each of which usually branch many times to form
an elaborate network (Fig 8). The dendritic field of most neurons extends for only a few hundred
8

microns (1000 microns equals 1 mm). In many cases the field is asymmetric, with a majority of
the dendritic field extending in one direction. Thus, many neurons of the cerebral cortex,
cerebellar cortex and olfactory bulb have long dendrites that extend upward to the surfaces of
these structures (Figure 8). That asymmetry is particularly pronounced for neurons that receive
the bulk of their synaptic input from a restricted set of axons. A good example is a mitral cell in
the olfactory bulb. It gives rise to a long dendrite that branches several times as it grows toward
the surface of the bulb and then at its end it breaks up into a series of very fine branches that
occupy a volume of tissue about 200-500 m in diameter. All of that branching occurs because
in the same volume of tissue are the axons of olfactory sensory neurons; those sensory neurons
respond to the presence of odorant molecules in the air and carry that information from the
olfactory epithelium of the nose to the olfactory bulb in the brain. And so optimize the level of
input they receive from olfactory sensory neurons, mitral cell dendrites form very elaborate
terminal tufts. In that arrangement of dendrite branches is the following lesson: dendritic fields
grow to optimize the level of input they receive from specific input axons.
Fig 7. For the majority of neurons three elements make
up the receptive surface: 1) Cell body or soma; 2)
Dendrite; 3) Dendritic spines. Synapses directly onto
cell bodies tend to produce the strongest effects on a
neurons activity. In addition the cell body contains the
nucleus of a neuron and all the organelles required for
protein synthesis and for packaging proteins. Synapses
onto the shafts of dendrites are common. By regulating
the length and location of dendrites a neuron can
determine which sources of synaptic input it will pay
attention to. On many neurons in the brain and spinal
cord, dendrites give rise to tiny protuberances called
dendritic spines. Not all neurons have spines but in
those that do spines are the sole recipients of excitatory
synapses. The number and shape of spines go a long
way to determining how responsive a neuron is to its
excitatory inputs.
DIFFERENCES IN THE SHAPE OF DENDRITIC FIELDS ARE IMPORTANT TO THE FUNCTION OF
NEURONS. Because dendrites are the major receptive surfaces of almost every neuron,
differences in the shape of dendritic fields allow two neurons to sample creatively from the
axons ending near them. Look, for example, at the neurons in Figure 8; neurons display
differences in dendritic shape that are characteristic of the region they occupy. That means the
shape of their dendritic fields is characteristic of neurons in one region and so to the practiced
eye, a picture of a Purkinje cell says we are looking at cerebellar cortex but those features of
dendrite shape differ markedly across regions of the nervous system.

Figure 8. Neurons differ in the shape of

their dendritic fields. That difference is
robust across different regions of the central
nervous system. Thus, Purkinje cells of the
cerebellar cortex look nothing like pyramidal
cells of the cerebral cortex and both of them
differ radically from ganglion cells of the
retina or mitral cells of the olfactory bulb.
Not illustrated in this figure is a corollary
neurons in the same region of the nervous
system, with cell bodies no more than a few
microns away from each, differ markedly in
the shape of their dendritic fields.
VARIATIONS IN DENDRITE SIZE AND SHAPE ARE ALSO COMMON WITHIN A SINGLE REGION OF
THE CNS. No region of the CNS has only one type of neuron in it; all have several types with
their own inputs and outputs and their own shapes. Because inputs vary among neurons in a
single region of the CNS, so do the shapes of their dendritic fields. To illustrate this principle, a
particularly good example is the population of retinal ganglion cells (one of these is labeled
simply, ganglion cell, in Figure 8). The ganglion cell illustrated in Figure 8 has a dendritic field
that is confined to a narrow region just above its cell body. From the shape of this field we can
predict with great confidence this neuron generates action potentials to the introduction of a
bright stimulus it displays an ON response. But move those dendrites to an equally narrow
region farther away from the cell body and the neuron takes on a very response because it gets a
very different input it responds to the removal of light and so we say it has an OFF response.
All of this happens because during development of the retina, ganglion cells give off and then
mold their dendritic fields to match a specific input. Again, the general lesson here is the
important thing to grasp: dendrites vary across populations of neurons because dendrites are the
major receptive element of most neurons. As inputs vary from one neuron to another, so do their
dendritic fields.
DENDRITIC SPINES ARE TINY PROTRUSIONS ALONG THE SURFACES OF DENDRITES. Many
dendrites give off short protrusions called dendritic spines. The part of the spine that arises from
the dendritic shaft is called the spine neck, whereas the part at the end of the neck is the spine
head. In some parts of the central nervous system the cerebral cortex, in particular - the length
of the spine neck and the size of the spine head vary considerably from one spine to the next,
even on the same dendrite (Figure 9). That difference in size and shape arises from a
fundamental feature of spines, namely their ability to grow out of a dendrite throughout the life
of a neuron and their ability to get larger under appropriate conditions (mainly when the synapse
they receive is particularly effective at depolarizing a neuron). You can very properly think of
dendritic spines as the major sites for excitatory synaptic transmission in the CNS and you will
come to appreciate spines as the major sites for changes in synaptic strength that underlie
phenomena such as learning and memory.

10

Fig 9. Single spines include a neck and a

head. Both of these structural features vary
dramatically along a fairly short segment of
dendrite. Some spines have long, skinny
necks and a small head whereas others have
short necks and big heads. Features of the
first group the ones with long necks can
change very quickly. Spines such as these
can appear in a matter of hours and
disappear just as quickly. Spines with short
necks and big heads are called mushroom
spines. They are a much more stable
population that persist and display little
structural change over a period of weeks.
SPINES DO NOT FUNCTION TO INCREASE THE SURFACE AREA OF A NEURON OR TO MAKE IT
POSSIBLE FOR A NEURON TO RECEIVE MORE SYNAPSES FROM OTHER NEURONS. One of the first
models proposed to explain the existence of spines was that of Ramon y Cajal in the late 1800s;
he proposed spines are necessary to increase the surface area for reception of synapses. For all
but one type of neuron in the mammalian CNS those would be Purkinje cells of the cerebellar
cortex this model was shown to be incorrect in the late 1950s, when electron microscopic
studies showed there to be plenty of space along the shafts of most dendrites available for axon
terminals to form synapse. And so we have come to appreciate in the last 60 years that dendritic
spines do not increase synaptic space, generally, but are instead the targets of specific kinds of
synapses. Dendritic spines exist as specialized regions for the reception of excitatory synapses
from axon terminals that release the neurotransmitter, glutamate. A neuron that gives rise
to dendritic spines receives all its excitatory synaptic input on those spines. Neurons without
spines also receive excitatory synapses from glutamate-releasing axon terminals but those
synapses are found on dendrites and cell bodies.
Fig 10. In this electron
micrograph of a dendritic
spine you can see its
large head and narrow
neck. The black arrow at
the base of the spine,
where it comes out of the
dendritic shaft (PCd),
and the open arrow in the
spine head point to actin
filaments. These
structural elements
provide spines with the
ability to change shape
very rapidly. The large
11

organelle in the spine head indicated by the small black arrow is called a spine apparatus. It is
a piece of smooth endoplasmic reticulum that serves as a receptacle and reservoir for Ca2+. This
spine receives a single synaptic input (large arrow) from an axon terminal.
DENDRITIC SPINES ARE A MEANS FOR CHEMICAL ISOLATION ALONG A DENDRITE. Spines
provide a neuron with thousands of compartments that are chemically isolated from their parent
dendrites. That chemical isolation is particularly the case for the intracellular concentration of
Ca2+. A single spine has the means to respond to the repeated influx in Ca2+ and to accumulate
that ion for a brief period, thereby raising the concentration of Ca2+ in the spine but not elsewhere
along a dendrite (Figure 11). You can think of each spine as a semi-autonomous unit that
responds independently to the synaptic input it receives. In this case, Ca2+ functions not so
much as a carrier of electric charge but as an intracellular signaling molecule. One major role of
Ca2+ is that of an activator of enzymes in the cytosol of a neuron, and by turning on those
enzymes, Ca2+ changes the effectiveness of synapses in the long term (for weeks, months or even
years). Thus, the ability of spines to accumulate Ca2+ works to make the synapses on spines
particularly easy to change to make them stronger or weaker and to do so very quickly and
for very long periods.
Fig 11. Influx of Ca2+ into a spine has little effect on the
Ca2+ concentration in the dendritic shaft because so little
of the ion concentration (less than 1%) makes it through
the spine neck into the dendritic cytoplasm. Most of the
Ca2+ is absorbed by Ca2+-binding proteins (CaB) and
stored in smooth ER, which in a spine is called the spine
apparatus. Repeated entry of Ca2+ into a spine through
cation channels or stimulated release from the spine
apparatus produces a well-confined increase in Ca2+
concentration. This increase triggers a broad range of
intracellular events that lead to long-term changes in
synaptic strength.
THE NUMBER AND THE SHAPE OF SPINES ARE NOT CONSTANT. Rapid changes occur in the
number of dendritic spines and in the sizes of individual spines in some parts of the nervous
system during learning and memory. These rapid morphological changes occur through
regulation of the rich actin cytoskeleton of spines (Figure 10); anything that promotes actin
polymerization in a spine causes it to increase in size whereas anything that promotes the
depolymerization of actin filaments causes a spine to shrink. And since polymerization and
depolymerization of action are in constant balance, one can be made dominant over the other
very rapidly; the result is a change in spine size that happens in a matter of a few minutes.
Slower, more permanent changes in the number of dendritic spines occur with normal aging
(Figure 12B) and are particularly dramatic in certain neurodegenerative disorders (Fig 12C).
Several forms of intellectual disability, such as Fragile X syndrome, and many forms of neuronal
degeneration, such as those present in Alzheimers Diseases, occur at least in part through loss of
dendritic spines or abnormalities in constructing and maintaining their shapes.
12

Fig 12. Comparison of neurons

from young (A) and old (B) animals
demonstrates a remarkable
difference in the density of dendritic
spines. In addition, forms of mental
retardation and certain
neurodegenerative diseases are
accompanied by a massive
reduction in spine density normal
in C is to the left, and pathological
cases are the three examples to the right.

AN AXON IS THE INTEGRATING AND CONDUCTING SURFACE OF A NEURON

AN AXON IS THE PART OF A NEURON THAT CARRIES INFORMATION FROM THE RECEPTIVE
SURFACE (USUALLY THE SOMA AND DENDRITES) TO THE TRANSMITTING SURFACE (USUALLY
THE AXON TERMINALS). Axons are specialized in most neurons to conduct action potentials
from the site of their initiation in the initial segment of the axon to all the terminals of that axon.
Most axons are at least several millimeters in length and most give rise to thousands of axon
terminals, and so an individual neuron devotes a great deal of energy to maintaining the integrity
of its axon. A healthy axon returns the favor by faithfully conducting action potentials into every
one of its many branches and all of its many axon terminals.
EACH NEURON GIVES OFF A SINGLE AXON. During the period of its maturation, a neuron may
give rise to more than one axon but as a neuron matures most neurons maintain a single axon that
grows to a specific target region or to a small set of target regions. From that simple statement
you can see the following are true for all axons: 1) Axons vary in length and in site of
termination. They can be as much as a meter in length or as short as a few dozen microns, all of
which depends on the role that specific neuron plays in the functional circuitry of a brain region.
2) The place to which an axon travels is specific for each type of neuron. For a particular type of
neuron, each individual neuron has a characteristic target this is a particular place in some part
of the nervous system to which it sends its axon. At that location, the axon forms synaptic
contacts with specific types of neurons, often at specific locations along the surface of those
neurons. Here is an example: in the cerebellar cortex are neurons called granule cells, the axons
of which form synapses with dendritic spines given off by a population of Purkinje cells. None
of this chaotic; means exist to change the specific pattern of contacts formed by any single
granule cell but those contacts are with a group of Purkinje cells. And the Purkinje cells have
their own targets outside the cerebellar cortex. By this strategy in which neurons form synapses
with specific target cells, information flows in an organized fashion through the nervous system,
from sensory input to motor and cognitive output.

13

Fig 13. Axons arise from

a cell body at a region
called the axon hillock and
the first region of the axon
is called the initial
segment. The initial
segment is the location
dedicated to integrating
information. Axons
usually give off several
branches and, as those
branches, reach specific targets, they break up into a large series of terminal regions. By this
arrangement a single axon forms thousands of synapses.
We need to think separately about the following three regions along the length of an axon: 1)
The region where it arises the axons initial segment; 2) Its long shaft; 3) Its many terminal
regions.
AN AXONS INITIAL SEGMENT GENERATES ACTION POTENTIALS.

Axons arise from a region of

the cell body referred to as the axon hillock (Figure 13). The first part of an axon, called its
initial segment, displays a distinct morphology, chemistry and physiology. Along an axon
covered with the insulating material of myelin, the initial segment is the first part of the axon,
left uncovered by myelin. But for all axons, including those that remain entirely free of myelin,
the initial segment is a region of specialization, at which most action potentials are generated.
Studies that began in the 1950s established a simple truth: the location along a neuron that is
most sensitive to electrical stimulation is the axons initial segment. Passage of current at an
initial segment that depolarizes a neuron by some 15 mV (from -65 mV to -50 mV) drives a
neuron to generate action potentials; at other locations along the cell body or along dendrites,
much greater currents and a much larger depolarization is necessary to generate action potentials.
What produces that much greater sensitivity at the axons initial segment is the presence of a
very high density of voltage-gated Na+ channels in its plasma membrane. Because of their
density in the plasma membrane of the initial segment, the voltage-gated Na+ channels operate as
a very sensitive positive feedback loop. A few will open in response to a relatively small
depolarization and, as they do, they allow Na+ to move into the initial segment and further
depolarize the membrane; that further depolarization opens more voltage-gated Na+ channels to
allow even more Na+ to enter and increase the depolarization, which opens more channels all
that proceeds until all voltage-gated Na+ channels are open and the membrane potential has
reached a peak value of +40 mV. That is the generation of an action potential. And the presence
of so many channels packed into a small space makes generation of action potentials much easier
at the initial segment; as a result, the threshold for generating action potentials is lowest here.
INTEGRATION IS THE CONVERSION OF SYNAPTIC POTENTIALS INTO ACTION POTENTIALS. We
say the initial segment of an axon is the integrating surface of a neuron because it is here the
passive changes in membrane potential produced at synapses become action potentials (if they
14

are EPSPs) or those passive, synaptic potentials inhibit the generation of action potentials (if they
are IPSPs). Synaptic potentials are analog signals in that they vary along a continuous scale
whereas action potentials are digital; an action potential either is (equivalent to 1) or it is not
(equivalent to 0). Thus, integration is the process by which a neuron converts an analog input
its many synaptic potentials into a digital output action potentials.
Fig 14. Axons are narrow those in mammalian
nervous system are as small 0.1 m in diameter
and seldom wider than 10 m but because they
are so long, most of the cytoplasm of a neuron is
found in its axon. At its terminal regions, an
axon breaks up into a series of progressively
smaller branches that end as a series of 1-2 mwide terminal boutons (or just plain ol
terminals). Axon terminals are specialized
regions that contain all the molecular and
cellular machinery necessary for one neuron to
communicate with another neuron. That
includes organelles unique to axon terminals,
called synaptic vesicles, an abundance of
mitochondria to provide energy and membrane
specializations that permit synaptic vesicles to
fuse with the plasma membrane and release their
contents.
MOST AXONS GIVE OFF NUMEROUS BRANCHES. As an axon extends to its targets, it gives off
branches at each of several possible points. These include the following:
1) Near the site of origin. Many neurons have only a locally branching axon and are referred to
as interneurons. They are important for local processing of information and restrict their axons
to the region of the neurons dendritic field. Even axons of great length (up to a meter in length)
usually give off local branches, called axon collaterals. They terminate on the receptive
surfaces of neurons that close to the neurons cell body.
2) Along the path of the axon. In some cases, neurons that send their axons to one distant target
send branches to other, closer targets. A good example of this type of branching is seen for the
neurons of cerebral cortex that send axons to the spinal cord. As this axon makes its way to the
spinal cord it gives off branches to several subcortical targets, each of which gives rise to many
terminals that synapse with neurons in those targets.
3) Where axons finally terminate they invariably break up into an elaborate axonal tree with
dozens of branches and thousands of bulbous expansions, called axon terminals (Figure 14). On
average a single neuron gives off thousands of axon terminals that collectively form 10,000
synapses. That does not mean a single axon contacts 10,000 targets because most often an axon
15

forms several synapses with each of its targets. In some cases a single axon forms several dozen
synapses with a single target cell as a mechanism to maximize its effect.
ACTION POTENTIALS THAT BEGIN IN THE INITIAL SEGMENT OF AN AXON REACH ALL ITS
BRANCHES AND ALL ITS TERMINALS WITHOUT EXPERIENCING A REDUCTION IN AMPLITUDE.

Integration is done at the initial segment and action potentials are generated because only an
action potential can travel down a long axon without loss of signal; an action potential is as big
in all the axons terminals as it is at the initial segment. Synaptic potentials, by contrast, have a
limited distance usually on the order of a millimeter or two over which they can travel
without losing most of their punch. That some axons in the nervous system are a meter long and
that the great majority are at least a few millimeters long means most neurons in the mammalian
nervous system must generate action potentials if they are to produce any change in membrane
potential at their axon terminals. The way an action potential propagates down an axon is
identical to the way it begins at the initial segment, which is through the opening of voltagegated Na+ channels. Recall those channels are at highest density in the plasma membrane of the
initial segment, but they are also present at lower density along the entire length of the axon.
And so current that enters at the initial segment, moves down the axon to depolarize the next
piece of the plasma membrane; that depolarization opens voltage-gated Na+ channels in that next
piece of the plasma membrane (Figure 15) to drive the membrane potential there to +40 mV.
Current entering at that piece then moves down the axon to the adjacent region and there that
regions voltage-gated Na+ channels open to drive the membrane potential there to +40 mV. All
of that means each tiny segment of an unmyelinated axon generates its own action potential so
that the next tiny segment is depolarized to generate its own action potential. Segment by
segment, the action potential moves down the axon and because it moves by opening voltagegated Na+ channels down the length of the axon, it never gets any smaller. What invades each
axon terminal is an action potential that reaches +40 mV.
Fig 15. Depolarization of a
segment of unmyelinated axon
opens voltage-gated Na+ channels
to initiate an action potential. Na+
influx carries current into an axon
that moves down the axon to the
next segment. There, the current
opens that segments own voltagegated Na+ to propagate the action
potential. Again, Na+ influx carries
current into the axon and, again,
that current moves down the axon to
depolarize the next segment and regenerate the action potential. By
this segment-by-segment
mechanism, an action potential
moves down an unmyelinated axon.
16

MYELINATED AXONS CONDUCT ACTION POTENTIALS MORE QUICKLY BY SALTATORY

CONDUCTION. The insulating material, myelin, wraps long segments of an axon of up to 1
millimeter in length but leaves a narrow gap between every pair of myelinated segments. Those
gaps are called nodes of Ranvier, and for all intents and purposes they are tiny (50 m-long)
regions identical to the membrane of the initial segment. For present purposes, the most
important similarity between nodes and the initial segment is their very high density of voltagegated Na+ channels. So what happens in a myelinated axon is periodic regeneration of action
potentials; current flowing into an axon at the initial segment moves passively down the axon to
its first node of Ranvier, where the current depolarizes the membrane of the node and causes it to
open its voltage-gated Na+ channels (Figure 16). The node regenerates the action potential.
Current entering at the first node then moves passively down the myelin segment to the second
node and, by depolarizing the membrane at that second node, forces open its voltage-gated Na+
channels. Down goes the current to the third node and then the fourth and then the fifth. Node
by node, then, the action potential jumps down the axon in a process called saltatory conduction
(from the Latin word, saltare, which means to jump). For reasons we will make clear in a later
lecture, myelin speeds up the flow of current down each myelin segment the current moves
much faster down 1 mm of a myelin segment than down 1 mm of an unmyelinated axon, even if
the axons are the same diameter. And so the speed at which an action potential moves down an
axon we call this the axons conduction velocity is much greater for a myelinated axon in
mammalian nervous system than it is for an unmyelinated axon.

Fig 16. An action potential initiated at the initial segment of an axon moves passively down the
first myelin segment to the first node of Ranvier. There, at the node, the depolarizing current
that entered at the initial segment forces upon the high density of voltage-gated Na+ in the
plasma membrane of the node. Current entering at the first node moves passively to the second
node and leads that nodes voltage-gated channels to open. Thus, the action potential jumps
from node to node in a process called saltatory conduction.

TRANSMITTING SURFACE SYNAPSES ARE FORMED BY AXON TERMINALS

SYNAPSES ARE POINTS OF FUNCTIONAL CONTACT BETWEEN TWO NEURONS. The term, synapse,
was coined by Charles Sherrington to indicate a location of functional communication between
two neurons. For the great majority of synapses in the mammalian nervous system that
communication requires the release of aqueous chemicals (neurotransmitters) by axon terminals
17

and receipt of those chemicals by receptive surfaces (cell body, dendrite or dendritic spine) on
another neuron.
CHEMICAL SYNAPSES POSSESS THREE REGULAR FEATURES. The great majority of chemical
synapses display a triplet of features that can be used to define them (Figure 17). They are the
following: 1) A presynaptic element usually an axon terminal that contains clusters of small,
synaptic vesicles and a location along the plasma membrane that is structurally and chemically
specialized for release of contents in those vesicles. The specialization of the presynaptic
membrane is called the active zone; 2) A synaptic cleft that is physical separation 20-50 nM
wide between pre- and post-synaptic elements; 3) A postsynaptic element usually a dendrite,
dendritic spine or cell body with a plasma membrane specialized for detecting the molecules
released by the presynaptic element. This region of postsynaptic specialization is called the
postsynaptic density (PSD). Guided by the presence of complementary proteins in the two
plasma membranes, the presynaptic active zone and the PSD are lined up perfectly across the
synaptic cleft. Such precise alignment insures that neurotransmitter released at the active zone
reaches the PSD rapidly and at high concentration.
Fig 17. A presynaptic axon terminal
possesses the molecular machinery to release
the contents of synaptic vesicles and then
retrieve the membrane of the vesicles so they
can be re-used. Release occurs in most
neurons as a response to action potentials as
they invade the axon terminal. Those
contents the neurotransmitter molecules
are released into the synaptic cleft and
diffuse across the short distance to the
postsynaptic membrane of a spine, dendrite
or cell body. Along the membrane of the
postsynaptic element are proteins that bind
neurotransmitter molecules and produce a
change in the postsynaptic neuron. This is
often a direct or indirect change in
membrane potential.
AQUEOUS NEUROTRANSMITTERS ARE THE MOST COMMONLY ENCOUNTERED MEANS FOR ONE
NEURON TO COMMUNICATE WITH ANOTHER NEURON IN THE MAMMALIAN CNS. Most
neurotransmitters are water-soluble molecules such as amino acids (examples are glutamate and
glycine), amines (serotonin, dopamine and norephinephrine), nucleotides (ATP and adenosine)
or peptides (short chains of amino acids). For the great majority of synapses, these aqueous
neurotransmitters are packed into tiny vesicles called synaptic vesicles, where they can be stored
and protected from degradation. Well-defined biochemical steps in each axon terminal produce
fusion of the neurotransmitter-filled synaptic vesicles with the plasma membrane of the axon
terminal. A key, initial step to all this is the invasion of the terminals by an action potential that
18

leads to opening of a second voltage-gated channel, that for Ca2+. Entry of Ca2+ begins a series of
changes in the membrane of synaptic vesicles and in the plasma membrane of the presynaptic
terminal, leading to fusion of the two membranes and the release of neurotransmitter into the
synaptic cleft. A single vesicle contains several thousand molecules of neurotransmitter; some
fraction of them released into the cleft diffuses the short distance to the plasma membrane of the
postsynaptic cell and there they bind to appropriate neurotransmitter receptors, many of which
are ligand-gated ion channels. By this process, an action potential that invades an axon terminal
and prompts the release of neurotransmitter from the terminal leads to a change in membrane
potential in the postsynaptic cell.
SUMMARY. This electrical view of a neuron is a very useful simplification that helps to explain
its structure. Ions unevenly distributed across the plasma membrane set up a resting membrane
potential that serves as a battery to store charge. The energy stored in the resting membrane
potential can be unleashed by opening channels that allow Na+ to enter the cell along its
receptive surface, first to depolarize the membrane it to threshold and then, at the initial segment
of its axon, to generate action potentials. Integration is the name we give to the conversion of
passive, analog signals of synaptic potentials to the active, digital signals of action potentials.
Again, that happens at the initial segment. The rest of the axon conducts action potentials so that
the amplitude of the potential change at all the axon terminals is the same as it was at the initial
segment. An action potential remains the same height throughout the length of an axon. Such a
large potential change is required to initiate the release of neurotransmitter stored in tiny vesicles
in each axon terminal. By binding to receptors in the plasma membrane of the axons target
cells, neurotransmitter leads to changes in the membrane potential of those targets. And so what
has gone on in one neuron the electrical flow of information leads to release of a chemical
signal that produces an electrical change in the next cell.

HOUSEKEEPING FUNCTIONS OF A NEURON

THE NEURONAL CELL BODY IS THE SITE FOR TRANSCRIPTION AND TRANSLATION. In addition to
its role as a receptive surface for synapses, the cell body of a neuron is the major center for all
housekeeping functions. Synthesis of proteins transcription of genes and translation of
mRNA and post-translational processing of proteins take place in the cell body because
all organelles for these functions are present there. You will notice that the size of the cell
body varies widely among neurons, both within a specific region of the CNS and across regions
of the CNS. This variation in the size of cell bodies is correlated with the length and diameter of
axons given off by neurons, which makes sense since more than 9/10ths of a neurons cytoplasm
and membrane is in its axon but axons have a very limited capacity for translational and no
mechanism for post-translational processing. Therefore, supporting and maintaining an axon and
all its terminals requires constant production of protein.
THE CELL BODY OF EVERY NEURON CONTAINS ITS NUCLEUS. Neuronal nuclei contain large
amounts of heterochromatin (Figure 18), most likely a reflection of the fact that beyond a
restricted period in development, a typical neuron leaves mitosis and divides never again. As is
true for all other cells in the body, a neurons nucleus is the site in which the genetic material is
19

stored. Transcription is its principal role and so control of transcription which genes to
transcribe and at what rate becomes the key to controlling what a neuron will do.
Fig 18. A schematic diagram of
a neuronal cell body illustrates
several key organelles the
nucleus, rough endoplasmic
reticulum and Golgi complex
are the places for transcription,
translation and
posttranslational
processing/packaging of
proteins. Other cytoplasmic
organelles include
mitochondria, for energy
generation, and lysosomes, for
the breakdown of lipid-rich
membranes. In addition, an
elaborate cytoskeleton
maintains the shape of a neuron.
RIBOSOMES ARE THE SITES OF
PROTEIN TRANSLATION IN A
NEURON. Neuronal cell bodies

possess an extreme density of

ribosomes, much like the
cytoplasm of other cells (e.g. liver and pancreas) that actively synthesize and secrete large
volumes of proteins and other products. Ribosomes are found freely but are most common in
stacks of rough endoplasmic reticulum. These stacks of RER in neurons are referred to as
Nissl bodies, named for the German investigator who discovered their presence in neurons. Of
the free ribosomes ones that are not attached to Nissl bodies the ones most actively studied
are found at the bases of dendritic spines, where the spines grow out of a dendritic shaft. Several
observations strongly indicate these spines are responsible for translation of proteins that are
highly concentrated in the spine, itself. By this strategic placement of ribosomes, dendritic
spines are able to exert control of translation at a local level. As the level of synaptic activity on
a spine changes it can rapidly adjust the rate of translation for proteins meant specifically for that
spine.
A RICH GOLGI COMPLEX MODIFIES PROTEINS AND PACKAGES THEM FOR TRANSPORT. As the
primary site of post-translational processing the Golgi complex is well developed in the neuronal
soma. Particularly important is glycosylation of proteins and their packaging into vesicles
used for transport and secretion. Transport vesicles move large amounts of protein down and
axon to replace those that have exceeded their shelf lives. Thus, the tactic used by neurons to
translate mRNA into protein in the cell body requires a well-developed Golgi complex to store
those proteins for movement down the axon.
20

MITOCHONDRIA ARE UBIQUITOUS COMPONENTS OF A NEURON. Neurons use oxidative

phosphorylation to produce a great deal of energy and they consume much of that energy just
keeping the correct ion concentrations across the membrane. A major player in that process is a
Na+/K+-ATPase that burns a molecule of ATP to move Na+ out of the cytosol and K+ back into
the cytosol. If for no other reason than the need to fuel this pump throughout the neuron, many
mitochondria are present from the cell body to the axon terminal.
NEURONAL CYTOSKELETON
A NEURONS COMPLEX SHAPE THE LENGTH OF ITS AXON AND THE BRANCHING OF ITS
DENDRITES AND THE FORMATION OF DENDRITIC SPINES REQUIRES THREE TYPES OF
ORGANELLES. Microtubules, neurofilaments (neuronal intermediate filaments) and actin
microfilaments contribute to the formation, maintenance and stability of a neurons complex
shape (Figure 19). They make up the neuronal cytoskeleton, which is a dynamic structure that
adapts throughout life to the changing neuronal environment. And so the organelles that make
up the cytoskeleton have to change rapidly and throughout the life of a neuron. An additional
consideration is this: most protein translation occurs in the cell body whereas very little of it
occurs in a mature axon, but the axon contains most of the membrane and most of the cytosol in
a neuron. That means something has to actively transport protein into the axon. Part of the
neuronal cytoskeleton is the structural element for transport of proteins and of organelles from
the soma, where they are made, into the axon.
Fig 19. Three organelles
make up the neuronal
cytoskeleton: 1) Microtubules
these resemble hollow tubes
in the cytoplasm of all parts of
a neuron; 2) Neurofilaments
thin, thread-like organelles
that form bundles, particularly
in axons and dendrites; 3)
Microfilaments or actin
filaments found beneath the
plasma membrane in all parts
of a neuron. All three
organelles, actin filaments in
particular, can change rapidly
in response to many signals.
MICROTUBULES AND NEUROFILAMENTS ARE THE PRIMARY DETERMINANTS OF NEURONAL
MORPHOLOGY. Microtubules are composed of and tubulin and of microtubule associated
proteins (MAPs) that differ in size and distribution along the neuron (high molecular weight
MAPs such as MAP-2 are present in the cell body and dendrites whereas low molecular weight
MAPs such as tau exist in axons). Neurofilaments, by contrast, are responsible for setting the
21

diameter of an axon. Neurofilaments are neuronal intermediate filaments, composed of four

principal proteins of differing weights (three are called neurofilament proteins) plus a couple of
associated proteins. The heaviest NF protein can be seen as a stabilizing element for the structure
of a neuron. Because the heavy NF protein has a long, heavily phosphorylated side-arm that
permits cross-linking with microtubules, the neurofilament dictates the spacing of cytoskeletal
elements in the axon, and thus the caliber of an axon.
MICROTUBULES ARE THE SCAFFOLD UPON WHICH STORAGE VESICLES ARE TRANSPORTED
ALONG AN AXON. To supply the axon and dendrites with proteins, membranes and mitochondria,
an active mechanism of axoplasmic transport moves storage vesicles and other organelles from
the soma to the tips of the neuron. This movement from cell body to axon terminal is called
anterograde transport. A similar transport mechanism, called retrograde transport, moves
worn out organelles and patches of membrane back to the soma for degradation by lysosomes
(Figure 20).
AXONAL MICROTUBULES ARE POLARIZED TO PRODUCE TIGHTLY REGULATED MOVEMENT OF
ORGANELLES ALONG AN AXON. The individual tubulin molecules form polarized filaments that
in axons are arranged with their plus ends toward the axon terminal and their minus ends toward
the soma. This polarization is exploited in directing traffic along the axon core. Separate
molecular motors (they are ATPases) move vesicles and other elements in anterograde direction
from soma to axon terminals or in retrograde direction from terminals back to the soma
(Figure 20). The molecular motors for anterograde transport are the kinesins; they attach to
storage/transport vesicles and to microtubules and, through the hydrolysis of ATP, move these
vesicles toward the axon terminal. Cytoplasmic dyneins are the motors used for retrograde
transport they attach to vesicles filled with worn out proteins and lipids and move them toward
the soma, where they are broken down by organelles called lysosomes.
Fig 20. All the key components
to the neuronal cytoskeleton are
pictured here. The number and
arrangement of neurofilaments
determines its diameter. Along
microtubules, storage vesicles
filled with newly synthesized
proteins are propelled toward
axon terminals by way of kinesin
this is anterograde transport.
Retograde vesicles are driven in
the opposite direction
retrograde transport by
cytoplasmic dynein. Signal
proteins in the membranes of
these vesicles determine whether
they will attach to kinesin or dynein.
22

SUPPORTING CELLS OF THE NERVOUS SYSTEM

THREE TYPES OF SUPPORTING CELLS OR GLIA ARE FOUND IN THE CENTRAL NERVOUS SYSTEM.
They are astrocytes (star-shaped supporting cells), oligodendrocytes (cells with few processes)
and microglia. For a bit more than fifty years, hundreds of thousands of medical students and at
least that many college students have been told there are ten times more glia cells in the CNS
than there are neurons. The folks who first said there was such a huge difference made up that
ratio, and those who have repeated it have done so without asking, is it true? Turns out it is
wrong, at least for humans. In our cerebral cortex the number of neurons is slightly larger than
the combined number of all glial cells; and in our cerebellum, neurons grossly outnumber glial
cells. For the human brain and spinal cord, as a whole, 90 billion neurons outnumber 89
billion glial cells.
OLIGODENDROCYTES ARE THE MYELINATING CELLS OF THE CNS. Two electrical properties of
a dendrite or an axon determine how easily and how quickly current can move. One of those is
internal resistance, which is set by the physical size of the dendrite or axon; the wider they are
the lower is their internal resistance. And the second is membrane resistance. In a dendrite or
along a bare axon, membrane resistance is a function of how many channels are present and open
(the greater the number of open channels, the lower is the membrane resistance). Many axons in
all sorts of vertebrates use a second means to increase membrane resistance; they invite
supporting cells to coat them in a phospholipid rich material called myelin. Axons in the brain
and spinal cord (the central nervous system) communicate with glial cells called oligodendrocyte
and induce them to form myelin (Figure 21). An oligodendrocyte gives rise to a few processes
(ergo its name) but each process divides repeatedly so that the oligodendrocyte, as a whole, gives
off something close to fifty terminal branches. Each of the terminal branches wraps itself
repeatedly around a segment of an axon that is typically 1 mm long. Therefore a single
oligodendrocyte can form myelin along a 1mm segment of fifty separate axons (Fig 21).
Fig 21. The arms of an
oligodendrocyte wrap themselves
around short segments of many,
nearby axons. The length of the
myelinated segments varies from one
axon to another but is normally
constant for a particular axon. Each
of the myelinated segments is
separated from those that come
before and after by a short stretch of
unmyelinated territory these are the
nodes of Ranvier.
SCHWANN CELLS MAKE MYELIN IN
THE PERIPHERAL NERVOUS SYSTEM.

A separate class of supporting cell,

called a Schwann cell, performs the function of myelinating axons in the peripheral nervous
23

system (nervous tissue outside the brain and spinal cord). And unlike an oligodendrocyte, which
provides myelin to segments of many axons, each Schwann cell myelinates only one segment of
one axon. One such myelinated segment is typically 1 mm in length (they can be much shorter)
whereas an axon can 1 meter in length, and that means 1000 Schwann cells must cooperate to
myelinate an axon of such a great length.
ASTROCYTES MAINTAIN THE EXTRACELLULAR ENVIRONMENT OF THE CNS. Star-shaped
supporting cells give rise to many fine processes that occupy the space between neurons. One
major target of astrocyte processes is the surface of brain capillaries (Fig 22); their processes
form large expansions, called end-feet on the capillary surface but they do not fully cover that
surface. Other astrocytic processes surround presynaptic and postsynaptic elements in a synapse,
and thereby isolated those elements from surrounding dendrites and axons. Astrocytes are able,
then, to take up excess neurotransmitter that has leaked out of a synaptic cleft. And they are
able to maintain the proper concentrations of K+ and water in the extracellular fluid. These
excess molecules and atoms move through an astrocyte and are pumped from end-feet into brain
capillaries.
Fig 22. Astrocytes give off long, branching
processes that terminate as astrocytic endfeet. Many end-feet attach themselves to the
surfaces of brain capillaries (arrows). As a
result, more than 3/4ths of the brain
capillary surface is covered by the end-feet of
astrocytes, not as a barrier to the diffusion of
molecules, but as a conduit for nutrients to
enter the CNS from its blood supply and a s
means to deposit excess K+ and water.

Axon

Astrocytic processes also form a rich plexus

around the cell bodies, axons and dendrites
of neurons. One estimate suggests astrocytes
and their processes occupy half the volume
of the rat cerebral cortex.

MICROGLIA ARE IMMUNE-COMPETENT CELLS IN BRAIN AND SPINAL CORD. Under normal
circumstances endothelial cells that line the capillaries of the brain and spinal cord form tight
junctions with one another to make sure cells and proteins in blood cannot make it into the CNS.
These tight junctions are the basis for a barrier between blood and brain that is called,
appropriately enough, the blood-brain barrier. Although infections of the CNS can prompt
immune cells of the blood called monocytes to open the blood-brain barrier and enter the brain,
the only resident immune-competent cells of the CNS are microglia. These cells lie in a resting
state until they are stimulated by chemical factors that signal nearby cell damage or that tell
immune cells of an invasion by bacteria or viruses or fungi. At that point, the microglia change
24

shape dramatically (Figure 23) and become phagocytic; they actively consume dead and dying
cells and they attack pathogenic invaders.
Fig 23. Microglia arise from the same
stem cells that generate all the cells of the
immune system. They are derived from a
different embryonic layer than all other
cells of the CNS (microglia arise from
mesoderm whereas neurons, astrocytes
and oligodendrocytes arise from
ectoderm) and they invade the CNS
before the blood-brain barrier forms. A
single microglia has an unusual shape,
with many processes, when it is at rest
(A). But when chemical messengers that
signal foreign invasion or tissue damage
reach that cell it rounds up to look
exactly like a macrophage of the immune
system. Microglia release their own
chemical messengers, some of which invite cells of the immune system to invade the CNS and
others of which attach to damaged or infected cells. And then they turn phagocytic and surround
chunks of dead neurons or entire invading microorganisms. Through their expression of highly
reactive compounds, including the gas, nitric oxide, they break down the proteins and nucleic
acids of cells they engulf.

STUDY QUESTIONS
1) Dynamic polarization was the name Cajal gave to the concept that one part of the
neuron does one thing while another part does something else. Often that difference in
function boils down a difference in ion channels inserted into the plasma membrane at
distinct sites along a neuron.
a) What kind of ion channel inserted into dendritic spines makes them the primary sites for
generating excitatory postsynaptic potentials (EPSPs)?
b) What kind of ion channel, inserted into an axons initial segment, makes the initial segment
the site for action potential initiation?
c) Where else along a myelinated axon do you find high concentrations of the same ion channels
as the one you identified in (b)?

25

2) The blood brain barrier is formed late in the development of the CNS by the formation
of tight junctions between endothelial cells of CNS capillaries.
a) Which glial cell type takes advantage of that late development to invade the CNS?
b) What role do astrocytes play in the formation of the blood brain barrier?

3) What are the three elements of the neuronal cytoskeleton and their primary roles?

4) In the familiar figure to the left we can see the

dynamic polarization of neurons:
a) For each of the four functional zones (e.g. reception,
integration, etc) tell us the part(s) of the neuron that
performs that function.

b) For each of the four functional zones indicate a type of

ion channel that is vital for that function.

5) Astrocytes are one of the three major types of supporting cells in the CNS.
a) What are the other two? Identify the functions of those two.

26

b) By surrounding the individual axons in a bundle, astrocytes are able to remove excess K+ from
extracellular fluid. What would cause the concentration of K+ to increase in the extracellular
fluid surrounding a bundle of axons?
c) The membrane potential of an astrocyte is a function of [K+] only. If the local concentration
of that ion increases by a factor 10 (from 3 mM to 30 mM), by how many mV does the
membrane potential of an astrocyte change? (Be sure to indicate if the change is in the + or
direction)? You should appreciate this question was part of a final exam that covered not only
lecture 1 but also the lectures on membrane biophysics and so you will not be able to answer it
until you have dealt with the material in lecture 2.
d) Beyond its role as a K+ scavenger, what other functions do astrocytes have?


6) To the left is an electron micrograph of a myelinated
axon.
a) Identify the cytoskeletal elements indicated by the arrow
and those indicated by the arrowhead.
b) What are the two electrical properties of the axon altered
by the presence of myelin?
c) Squid use large axons to conduct action potentials rapidly.
That increase in diameter of an axon affects which two
electrical properties?

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