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CHAPTER 1: THE STRUCTURE OF A NEURON

The fundamental basis for all nervous system function is the neuron. Humans have some 95

billion of them in their brains and spinal cords and together they make possible all sensation,perception, movement and memory. As you will see in what follows over the next several

months, there is no such thing as a typical neuron. There is more variation among neurons than

among all other cell types in all other organs, glands and tissues in a mammalian body. One

simple fact makes this clear: of the 27 thousand genes in the human genome, almost 20 thousand

are expressed by some group of cells in the nervous system. Yet we must start with the default

characteristics of a neuron, the things that 95% of them display, 95% of the time, in order for us

to deal with the vital differences that come later. And so for a fundamental understanding of a

neuron we can divide what is known into two groups of data:

1) Each neuron maintains a complex shape in which separate regions perform distinct

functions. A typical neuron has many processes, some of which are most active in the reception

of information from other neurons and one that is responsible for transmission of information to

other neurons. Between reception and transmission are regions of a neuron that integrate and

conduct information. This division of labor – so apparent in the structure of individual neurons –

lead Ramon y Cajal to speak of the dynamic polarization of neurons (Figure 1).

2) Neurons possess organelles found in other cells but neurons have them in particular

abundance. These organelles include the machinery for extremely active protein synthesis andpackaging – in that neurons closely resemble secretory cells of the liver and pancreas – and they

possess an enormous number of cell junctions by which they communicate with other neurons.

DYNAMIC POLARIZATION

Dynamic polarization is a useful generalization that accents the anatomical and functional

specialization of a neuron. The term polarization is used because information tends to flow

from one end or pole of the neuron to another in most neurons, most of the time. We will

encounter significant 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. Thus a neuron is anatomically and functionally

polarized – reception at one end and transmission at the other. All of this is dynamic because the

strength and content of input and output varies from one moment to the next.

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Reception is a matter of taking in information; and for the vast majority of neurons that

information comes from other neurons. The principal parts of a neuron that receive inputs

from other neurons are its cell body and its dendrites. Many neurons, but not all, give off many

tiny protrusions from their dendrites called dendritic spines. These, too, are receptive parts of aneuron. We will see that more than just cell bodies, dendrites and dendritic spines are able to

receive information but the three make up the great majority of receptive regions for a typical

neuron.

Integration is a process in which the many small changes produced by reception of information

along dendrites and the cell body – together they are called synaptic potentials – can come to

produce a brief but powerful change called an action potential (see below for a fuller explanation

of these terms). That integration occurs at the axon hillock – where the cell body gives rise to a

neuron’s one axon – and the first part of the axon, called its initial segment. The rest of the axonconducts action potentials from the initial segment to all the axon terminals. And then at the

many axon terminals given off by an axon, information is transmitted to the next set of neurons.

That means the transmitting surface of a neuron provides the input to the receptive surfaces of

many other neurons.

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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. Thetwo 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 usually chemical – transmission from one neuron toanother requires the release of chemical messengers called neurotransmitters.

DYNAMIC POLARIZATION UTILIZES A SWITCH FROM CHEMICAL TO ELECTRICAL SIGNALING. Both the

reception of information from other neurons and the transmission of information to other

neurons require the use of chemical messengers in most parts of the nervous system. That is,

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E LECTRICAL

C HEMICAL



chemical signaling is used at the two ends of a dynamically polarized neuron, where information

flow is from one neuron to another. But within a single neuron – along its receptive, integrating

and conducting surfaces – information flow is electrical in nature. As we will see in some detail,

a neuron uses changes in voltage to carry information from one place – the receptive surface, for

example – to another place, such as the integrating surface. This switch from chemical toelectrical and back to chemical is made hundreds of thousands of times every day for each of the

80 billion neurons in a person’s central nervous system.

An understanding of polarization requires some appreciation of the electrical properties of

a neuron. The first principle to grasp is the presence of a plasma membrane that separates

cytoplasm for extracellular fluid (Figure 2). The two fluids have very different concentrations of

ions. Four ions – the cations, Na+, K+, Ca2+ and the anion, Cl- - stand out as most important fortheir roles in establishing and changing the electrical properties a neuron. The uneven

distribution of ions and the selective leakage of K+ across the membrane produce a voltage

difference across the membrane – this is called the resting membrane potential. For most

neurons the membrane potential is around -70 mV, which means intracellular fluid is 70 mV

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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+ , specifically the forty-fold

higher concentration of K + on the inside and the ten-fold

higher concentration of Na+ on the outside. Present in the

membranes of neurons are proteins that form selective

channels for the flow of an ion from the region of lower

concentration to the region of higher concentration. Thus,

K + flows from cytoplasm to extracellular fluid through a

specific set of constantly open leak channels. That

movement of K + deposits excess positive charge in

extracellular fluid and leaves behind negative charge in

cytoplasm. The result is a voltage difference between

cytoplasm and extracellular fluid that ranges from -60 mV to

-75 mV. This voltage difference is called the resting



more negative than extracellular fluid. The membrane potential is the basis for electrical

signaling within an individual neuron. A typical neuron receives contacts from other neurons

called synapses, most of which lead directly or indirectly to changes in the permeability of one

or more ions across the membrane. That change in ion permeability and the change in

membrane potential it produces will permit information to flow from a neuron’s receptivesurface to reach ultimately its transmitting surface. What matters for any one synapse – what

will make it move the membrane potential into more positive or more negative values – are the

ions allowed to enter or leave when that synapse is active (Figures 3 and 4).

Synapses define the functional divisions of a neuron. When we speak of receptive surfaces

along a neuron we most often mean surfaces that receive contacts from other neurons. The point

of contact between two neurons is called a synapse. 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 thousands of synapses from hundreds of other neurons –

figure out what they mean and carry that information to other neurons by forming synapses with

those neurons. Most of the one trillion synapses in the human brain and spinal cord are

chemical, in that they utilize the release of a chemical messenger from the transmitting surface of

one neuron to produce a change in the receptive surface of a second neuron. That change in the

receptive surface of a neuron is most often electrical. And to a first approximation the electrical

change can make the receptive surface less negative – it can briefly change the membrane

potential of a neuron from -70 mV to -68 mV – or it can make the membrane potential more

negative (e.g. take it from -70 mV to -72 mV). A change in membrane potential that makes a

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Fig 3. If Na+ is allowed to enter

the cell, a depolarization occurs.

This moves the membrane

otential away from -70 mV to a

less negative state (for example

-60 mV). Because each

depolarization moves the

membrane potential closer to a

value at which an action

otential will occur, it is called

an excitatory postsynaptic

otential (EPSP).



neuron less negative is called a depolarization and because, as we will see, this makes a

neuron more excitable, a depolarization at a synapse is called an excitatory postsynaptic

potential (EPSP). An opposite change – one that makes a neuron more negative – is called a

hyperpolarization. Because hyperpolarizations make a neuron less excitable, they are called

inhibitory postsynaptic potentials (IPSP). Figures 3 and 4 make an important point that theseopposite changes in membrane potential require the movement of different ions across the

membrane. Depolarization (EPSP) occurs through the inward flow of Na+ from extracellular

fluid to cytoplasm, whereas hyperpolarization (IPSP) typically occurs through the inward flow of

Cl-.

Synapses that produce EPSPs can depolarize a neuron to a value called threshold. When

excitatory synapses drive the membrane potential of a neuron from -70 mV to something close to

-50 mV, the relatively weak and passive changes in voltage become very robust and active

(Figure 5). The membrane potential goes from -50 mV to +40 mV and then comes back down to

and below resting membrane potential, all in a millisecond. This is an action potential. In

most healthy neurons action potentials begin in one region – the axon hillock and initial

segment of a neuron – and then move (they are conducted) to all parts of a neuron. The

reason we called EPSPs excitatory is for their ability to make it more likely a neuron will

generate an action potential; and IPSPs are inhibitory because they make it less likely a neuron

will generate an action potential. With these electrical events in mind – and they will be the

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Fig 4. Some 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 call

hyperpolarizations inhibitory

postsynaptic potentials (IPSPs).



subjects of their own, later chapters – we can turn to the structure of neurons and look for

specialized regions that receive and integrate synaptic inputs into action potentials, conduct

action potentials and then transmit the information in action potentials to other neurons.

Fig 5. Electrical potentials recorded from a neuron can be passive and relatively weak, such as

those seen in A. Both E1 and E2 are excitatory postsynaptic potentials. In combination those

weak synaptic potentials can bring the membrane to threshold (B& C), at which point the

membrane depolarizes all the way to +40 mV and returns to resting level in the space of one

millisecond. These brief, robust changes in membrane potential are called action potentials.

Synapses that produce inhibitory postsynaptic potentials keep the membrane potential away

from threshold and can, therefore, prevent a neuron from generating action potentials (D).

A SUMMARY OF FUNDAMENTAL ELECTRICAL PROPERTIES ACCENTS THE FLOW OF INFORMATION BOTH

BETWEEN NEURONS AND WITHIN A NEURON; AND IT FURTHER ACCENTS THE REQUIREMENT OF A CHANGE IN

MEMBRANE POTENTIAL FOR EITHER TO OCCUR. What dynamic polarization tells us is the switch in

every neuron from gathering to integrating then conducting information relies on electricity – a

voltage change in a neuron – whereas transmitting information requires the use of chemical

messengers in most parts of the nervous system. With the basic electrical and chemical elements

in place we can examine a typical, dynamically polarized neuron that permits each part to

perform a specific function.

RECEPTIVE SURFACES OF A NEURON

The major receptive surfaces of a neuron include its cell body (or soma), its dendrites and, for

many neurons, the tiny expansions that dendrites give off called dendritic spines (Figure 6).

Each of these plays an important role in controlling the generation of action potentials.

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A B C D



The importance of the cell body for neuronal communication lies in two features:

The cell body gives off all the neuron’s processes. Those 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 element of a neuron (Figure 6).

For most neurons the cell body is, itself, a receptive surface, in that it, too, is a target for

synapses formed by other neurons. What varies from region to region in the nervous

system – and from one cell type to another in a specific region – is the nature of synapses

formed on the cell body. Cell bodies of some neurons receive both excitatory and inhibitory

synapses – that is, EPSPs are generated at some axo-somatic synapses and IPSPs are formed

at other axo-somatic synapses. But many neurons receive only inhibitory synapses on their

cell bodies. The same is true for dendrites. Those on some neurons receive both excitatory

and inhibitory synapses whereas dendrites on other neurons receive only inhibitory synapses.The critical variable is the presence of dendritic spines. Neurons without spines on their

dendrites use the other receptive surfaces – both dendrites and cell body – to gather both

excitatory and inhibitory inputs, whereas neurons with spines use them for excitatory input

and reserve dendrites and cell body for inhibitory input.

Location is one, major factor in the strength of a synapse . The change in membrane potential

produced at a synapse grows weaker with distance ; and since a principal purpose of a synapse is

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Fig 6. 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 effectson a neuron’s 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



to control the membrane potential at the axon hillock and initial segment (where an action

potential originates) the closer it is to the axon hillock the stronger it will be. For that reason,

alone, synapses onto the cell body are viewed as particularly effective in either exciting a neuron

to generate action potentials or inhibiting a neuron from doing so. A change in membrane

potential also slows down with distance (again, see Chapter xx). For that reason, synapses ontocell bodies are often used in the central nervous system for transmitting information that is time

sensitive. One example is seen in two locations in the auditory brainstem, where the time it

takes a set of synapses to generate an action potential (this is called the synaptic delay) has to be

the same from one moment to the next. Those synapses are found in large numbers on the cell

bodies of their target neurons, thereby making them very effective in producing action potentials

with the same synaptic delay every time they are active.

The cell body of a typical neuron gives rise to several processes called dendrites. Each

dendrite usually branches many times to form an elaborate network; the total extent of all the

dendrites given off by a neuron – this is called its dendritic field – is as complex as the branches

of a large tree. The dendritic field of most neurons extends for only a few hundred microns

(1000 microns equals 1 mm) and is, in many cases, asymmetric, with a majority of the dendritic

field extending in one direction. Examples include neurons of the cerebral cortex, cerebellar

cortex and olfactory bulb with long dendrites that extend upward to the surfaces of these

structures (Figure 7).

Differences in the shape of dendritic fields are important to the function of neurons because

those differences allow two neurons in separate regions of the CNS to sample creatively from the

axons ending near them. Look, for example, at the neurons in Figure 7 – neurons display

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Figure 7. Neurons differ in the shape of their dendritic

ields. That difference is robust across different regionsof the central nervous system. Thus, Purkinje cells of the

cerebellar cortex look nothing like mitral cells of the

olfactory bulb or ganglion cells of the retina.

Differences in structure are partly a matter of which

genes each type of neuron expresses and, therefore,

which molecules it responds to during its development.

Structural differences are also a matter of which axons

terminate on a dendrite. As those axons vary in location

rom one region to another so will the shape of the



differences in dendritic shape that are characteristic of the region they occupy. That means the

size of the cell body and the shape of the dendritic field is characteristic of neurons in one region

– to the practiced eye, a picture of a Purkinje cell says we are looking at cerebellar cortex – but

those features of size and shape differ markedly across regions of the nervous system. A

retinal ganglion cell has a much smaller dendritic field, typically confined to a narrow band, anda mitral cell of the olfactory bulb has a characteristic tuft of branches at the end of its major

dendrite.

DIFFERENCES IN THE DENDRITE STRUCTURE ARE FOUND NOT ONLY AMONG NEURONS IN DIFFERENT

LOCATIONS BUT ALSO AMONG NEURONS IN A SINGLE REGION OF THE CNS (FIGURE 8). A very clear

example of these differences is seen in the cerebral cortex, where two general types of neurons

populate this entire region. One type is called pyramidal cells because of the triangular shape of

their cell bodies. These neurons typically give rise to a long, ascending dendrite that arises from

the apex of the cell body (which is why it is called an apical dendrite) and a set of dendrites at

the base of the cell body (erego basal dendrites). At a distance of only a few microns from the

cell body of a pyramidal cell can be the cell body of a type called stellate cells. This type of cell

is missing an apical dendrite and often gives rise to a set of dendrites that extends outward in all

dimensions, much like the light rays from a star. As we will see in some detail later these two

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Figure 8. Two neurons in the mammalian cerebral cortex

differ markedly in the shape of their dendrites even though

their cell bodies are only 100 µm apart. The pyramidal

cell on the left has a triangular cell body, a long apical

dendrite that ascends to the surface of the cortex and a set

of basal dendrites that radiate away form the cell body.

Next to it is a type of neuron, known loosely as stellate

cells (because some of their members have star-shaped

dendritic fields). These neurons have rounded cell bodies

that give rise to a chaotic tuft of dendrites – they have no

apical dendrite. Such robust structural differences

correlate well with variations in the development of these

two types early in life and with very different functions

throughout life. Equally clear differences in structure and



types of cells arise from very different progenitors and reach their final position in the cerebral

cortex along different paths. They also perform very different functions, and so they are an

excellent example of how different neurons in a single region can be. But they are not the only

example. Most regions of the central nervous system include more than a single type of neuron

and some regions contain as many as a few dozen types with distinct morphologies.

The shape of the dendritic field is the result of growth and branching of dendrites during

development. Controlled partially by a genetic program and partially through the influence of

input from other neurons, the shape of a neuron’s dendritic field is an individual property. No

two dendritic fields are the same. The contribution of normal development to the shape of

dendrites can be seen in Figure 8. Notice at the day of birth (day 0), this particular type of

neuron in rat cerebral cortex, called pyramidal cells, starts off with some basic features that we

presume to be genetically programmed. If neurons at this age were taken from the cerebral

cortex and grown in culture they would maintain this type of simple dendritic field, but left inplace for three weeks they take on an elaborate shape. What guides that growth in all its details

is the interaction between dendrites and axons that come into contact with them.

Fig 9. Dendrites of pyramidal cells in the cerebral cortex of neonatal rats grow dramatically in

the first three weeks of postnatal life. At the day of birth (day 0) dendrites are short and

unbranched but three weeks later the dendrites are more numerous, longer and much more

elaborate. The original, simple shape is a matter of dendritic growth guided by diffusible

proteins secreted from the surface of the cortex. Subsequent growth and the specific sites of

branching is more a matter of dendrites interacting with axons that have entered this region.

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Axon input shapes dendrites. Because axon terminations tend to be orderly in the CNS –

axons often end in specific layers or clusters – the shape of a dendrite says something about it

selectivity. From which axons does a specific neuron select its input? Two examples from

Figure 7 will make the point that dendrites grow in response to their synaptic input. Mitral cellsof the olfactory bulb have elaborate tufts of dendrites restricted to a particular layer and to a

specific region in that layer called a glomerulus. That tuft grows to occupy the full volume of a

glomerulus because into each glomerulus grow the axons of olfactory sensory neurons, carrying

with them information about odorant molecules in the air. Thus, the functional matching of

olfactory input axons with mitral cell dendrites determines the shape of those dendrites. A

similar effect is seen in Purkinje cells of the cerebellar cortex. Their dendrites are not only

restricted to a particular layer in the cerebellar cortex called the molecular layer but also to a

specific thickness. Purkinje cells dendrites are almost two-dimensional. They are a few hundred

microns high and several hundred microns wide but only a few microns in depth. What guides

the development of such an unusual dendritic field is its interaction with the Purkinje cells’

principal input, called parallel fibers. These axons run at right angles to the major axis of the

dendrites. As many as 100,000 parallel fibers contact a single Purkinje cell but each parallel

fiber forms only a single synapse with any Purkinje cell. With those as rules of parallel fiber to

Purkinje cell communication, each Purkinje dendritic field maximizes its input by growing tall

and wide while remaining very thin. Input determines shape.

DENDRITIC SPINES RETAIN THE ABILITY TO CHANGE SHAPE IN ADULTS.

Dendritic spines are the sites of specific types of synapses. Many dendrites give off short

protrusions called dendritic spines that serve as popular sites for synaptic input. Whereas the

original observations of spines were met with considerable skepticism – some investigators in

early 1900’s thought they were artifacts of the methods used to stain neurons – the first use of

electron microscopes to study neurons in the mid 1900’s conclusively demonstrated their

existence on many neurons of the mammalian brain. Over that same period and for the same

reasons the first hypothesis of spine function, that they exist to increase synaptic space on a

neuron, was thrown into doubt when long stretches of dendrites were shown to be free of

synaptic input. We now appreciate that spines are sites for specific types of synapses – those

that produce EPSPs. If a neuron possesses spines on its dendrites all synapses that generate

EPSPs will occur on spines. Neurons without spines receive excitatory synapses on their cell

bodies and dendrites. For neurons with spines, synapses on cell bodies and dendrites are

restricted to those that generate IPSPs.

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Spines are constructed of necks and heads. 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 (Figure

9). On the head of the great majority of spines is a synapse from an axon terminal. Some spines

receive two such synaptic contacts and reports of spines free of any obvious synaptic contact are

rare but not unheard of. A common feature in the neck of a spine is a cluster of ribosomes thatrepresent the sites of translation for proteins specific to the spine (Experimental findings).

Equally common to the spine head is membranous structure called the spine apparatus (Figure 9,

outlined arrow). This organelle is a piece of smooth endoplasmic reticulum, notable for its

ability to sequester Ca2+ by pulling it out of the cytoplasm and then to release it when

appropriately instructed.

Fig 9. 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 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.

The shape of necks and heads vary markedly from one spine to another. The length of the

spine neck and the size of the spine head differ considerably from spine to spine, even on the

same dendrite (Figure 10). Those differences mean a great deal to the long-term prospects of a

spine. Because these parts of a neuron are made and retracted constantly those that are stable

over a long period are in the minority. All of the stable spines have large heads and thick necks

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– they are called mushroom spines for this reason. Those with thin necks and small heads are

unstable, either because they were just formed and might be on their collective way to becoming

large and stable or because having been formed some time earlier they are on their way toward

elimination. As a result you can think of the picture in Figure 10 as a snapshot of one segment

of a dendrite. Had the same segment been examined two hours earlier or two hours later thesmaller spines would have either grown in size as they became permanent features of the

dendrite or they would have been retracted entirely.

Spines provide a neuron with thousands of compartments that are chemically isolated fromtheir parent dendrites. At many synapses that produce EPSPs, both Na+ and Ca2+ enter the

cytoplasm. Entry of Ca2+ is particularly important because of that ion’s ability to trigger a wide

range of long-term changes in a neuron. Here is where the unusual shape of a spine – that it is

connected to the dendrite shaft by a constriction – comes into play. A single spine has the means

to respond to the repeated influx in Ca2+ and raise the local concentration of that ion without

producing a large effect in any other part of a neuron (Figure 11). Experiments can determine

Ca2+ concentration by the intensity of a signal produced when the ion binds to a dye sensitive

only to it. Those experiments reveal that most Ca2+ entering a spine gets pumped into smooth

endoplasmic reticulum (the spine apparatus) or out of the spine entirely. Very little enters the

dendrite from which the spine arose. By this mechanism the Ca2+ concentration rises in a very

tightly localized region for a very short period of time. Thus each spine appears to work as a

semi-autonomous unit that responds independently to the synaptic input it receives.

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Fig 10. 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

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 and stored in smooth ER, which in

spines is called the spine apparatus. Ca2+ can enter the

spine cytoplasm either through channels in the plasma

membrane or by stimulated release from the spineapparatus. Separately or together they produce a very



The number of spines is not constant. Rapid changes in the size and shape of spines and the

addition, retraction and selective stabilization of spines occur throughout life (Figure 12). If the

same dendrite is visualized repeatedly over a period of weeks, spines are seen to come and go on

a regular basis. Both growth and retraction speed up significantly along dendrites of neurons

that are involved in the acquisition of new skills – a motor program that allows an animal to stay

on a moving bar – or new knowledge – spatial memory of a place that is safe or inviting. What

remains is the selective stabilization of a specific population of new spines. Figure 12 is taken

from a report of one such experiment done by G. Yang and colleagues. Dendrites from neurons

in the primary motor area of mouse cerebral cortex were imaged before and after motor training.

Growth of new spines occurred at rates much higher than those seen without training, but so did

removal of most of them. The resulting stable population of newly acquired spines across the

population of motor cortical neurons is thought to represent a structural basis for learning and

memory.

Fig 12. In an experiment that required mice to learn a motor task – how to stay on a tube that

rolled at varying speeds – dendritic spines were visualized in a part of the cerebral cortex that

executes voluntary movements (primary motor cortex). Neurons were engineered to produce a

brightly fluorescent signal so that their dendrites and spines could be visualized repeatedly over

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Target selection is a major task each axon faces during its development and, when properly

executed, it leads to the proper functioning of an entire system of neurons. An example is

the proper localization of a visual target, such as a car approaching yours at high speed.

Your abilities to determine its location and compute its path – will it intersect with your

own path? – depend on the precise of termination of axons from retina to brain and thenthrough several synaptic stations in the brain.

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. These two – the axon hillock and initial segment – are the

locations 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 three regions along an axon: 1) The region where it arises –

the axon hillock and initial segment; 2) Its long shaft; 3) The terminal regions. The axon hillock

and initial segment are the regions referred to earlier as the integrating surface of a neuron

whereas the axon proper conducts information from the hillock to all the axon’s terminal

regions. The terminals, then, are the sites of transmission, where the electrical events all along

the axon turn into the chemical relay of information to all the target neurons of that axon.

Integration of synaptic potentials takes place at the origin of the axon. Axons arise from a

region of the cell body referred to as the axon hillock (Figure 13). It and the very first part of

an axon, called the initial segment, display a distinct morphology, chemistry and physiology.

The initial segment got its name from the fact that along axons covered with insulating material

called myelin, the initial region of the axon is devoid of myelin. That initial segment and the

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adjacent axon hillock are characterized by the presence of a very high density of voltage-

sensitive Na+ channels inserted into the cell membrane. Because of the insertion of so many

of these channels into the membrane, the axon hillock and initial segment are most sensitive to

changes in membrane potential. As we saw in Figure 5, depolarization that reaches a threshold

value (typically when a depolarization raises the membrane potential from -65 mV to -50 mV)the result is an action potential. Under normal circumstances in most neurons action potentials

begin in the axon hillock and initial segment because threshold here is lowest. Integration, then,

is a matter of action potential initiation and that happens most of the time in most neurons at the

axon hillock and initial segment.

Change and loss of information takes place with the generation of action potentials.

Integration means that passive changes in membrane potential produced at synapses can become

action potentials (if they are EPSPs) or prevent action potentials (if they are IPSPs). The

combined effect of synaptic potentials has the virtue of varying continuously in size, not just

from + to - but also from less than 0.1 mV to more than 20 mV. They are an analog signal of

activity in all the synapses on a neuron in any one millisecond. The axon hillock and initial

segment convert all of that into a digital signal – either by producing an action potential (1) or by

preventing an action potential (0). The high density of voltage-gated Na+ channels in those

regions performs this function by either opening as a group (action potential is initiated = 1) or

18

Fig 14. Axons are narrow – those in

mammalian nervous system are as small

0.1 µm in diameter and seldom wider

than 10 µm – but because they are so

long, most of the cytoplasm of a neuronis 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 µm-wide 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



staying closed as a group (no action potential = 0). Information is lost during integration at

the axon hillock-initial segment. Integration is done and action potentials are generated

because only they allow information to make it down a long axon without fading entirely.

Passive, synaptic potentials have a limited distance – usually a few hundred microns – over

which they can travel without losing all of their punch. That some axons in your nervous systemare a meter long and that the great majority are at least a few millimeters long means most

neurons in the mammalian nervous system must integrate synaptic potentials to generate

action potentials if they are to have any effect on their targets. But action potentials do not

vary in size. They truly are digital in the sense that an action potential is present or it is not – it

is 1 or 0 and never 1.2 or 0.7 or -0.3 or any other value. As a result information in action

potentials is restricted to the rate of their generation (how many per second) and their pattern

(clustered into five closely-spaced action potentials or separated into individual and widely space

action potentials). Thus the range of possible signals is much more limited with action potentials

than with synaptic potentials and neurons adopt action potentials only if they are forced to by thelimits to the distance a synaptic potential will travel.

As a typical axon extends to its most distant target, it gives off branches at each of several

possible points (Figures 13 & 14):

Many neurons have axons that go no farther than their dendritic fields. These neurons

with locally branching axons and are referred to as interneurons. They are important for

local processing of information and often inhibitory in function. But they are not the only

neurons that form synapses with nearby neurons. Even axons of great length usually give off local branches that synapse upon neurons very close to their parent cell bodies. These local

branches, called axon collaterals, are one means for a neuron to engage its neighbors in the

functions it performs.

In many cases, neurons that send their axons to one distant target send branches to

other, closer targets. A good example here is the population of neurons in the cerebral

cortex that send their axons to the spinal cord (they are referred to as corticospinal neurons).

On their way to the spinal cord the axons of corticospinal neurons send branches to several

other parts of the brain, often as part of a mechanism for engaging other regions incontrolling a function, such as the generation of voluntary movements.

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 hundreds of axon terminals that collectively form

19



thousands of synapses. The range of termination patterns is extreme. A single axon can

give off several dozen axon terminals, all of which terminate on the cell bodies of a couple of

neurons or an axon can give off several hundred terminals to contact a hundred target

neurons in each of two or three separate locations.

As a general rule action potentials that begin in the hillock of a healthy axon invade all terminals

of that axon. Action potential failures are rare if an axon is part of a healthy neuron. This robust

electrical change in the plasma membrane has its origin in the events that take place in the axon

hillock and initial segment and that the propagates down the axon to all its terminals. What

happens in each terminal is a process that converts the electrical change into a chemical event.

TRANSMITTING SURFACE – SYNAPSES FORMED BY AXON TERMINALS

Synapses are generated where axon terminals of one neuron contact the receptive surfaces

(dendrites, spines and cell bodies) of other neurons. The term, synapse, was coined by Charles

Sherrington to indicate a location of functional communication between neurons. For the

20

Fig 20. 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 chan e in membrane



great majority of synapses in the mammalian nervous system that communication requires the

release of aqueous chemicals, called neurotransmitters, by axon terminals and receipt of those

chemicals by receptive surfaces (cell body, dendrite or spine) on another neuron.

Complexity of function requires chemical synapses. One can argue the complexity of brainfunction arises not from the number of synapses but from the presence of chemical synapses.

The great variety of molecules used as neurotransmitters and the extreme variety in

receptor molecules selective for any one of those neurotransmitters makes the brain

complex. More than 100 aqueous molecules have been assigned some role as neurotransmitters

and for some neurotransmitters thousands of distinct receptor types may exist.

Nevertheless, chemical synapses possess several regular features that define them (Figure 21).

These include:

1) A presynaptic element – usually an axon terminal – that contains clusters of small,synaptic vesicles and a membrane that is structurally and chemically specialized for

release of contents in those vesicles.

2) A synaptic cleft or space 10 nM wide separating pre- and post-synaptic elements.

3) A postsynaptic element – usually a dendrite, dendritic spine or cell body – with a

membrane specialized for detecting the molecules released by the presynaptic element.

21

Fig 21. An electron micrograph of a synapse

between an axon terminal and dendritic spine

shows the presence of pre- and post-synapticorganelles. In the axon terminal is a cluster of

synaptic vesicles and a mitochondrion (arrow).

Where the vesicles come very close to the

resynaptic membrane is a region called the

active zone. Vesicles in the active zone are

ready to be released. Separating pre- and post-

synaptic membranes is the synaptic cleft. The

ostsynaptic membrane of the spine displays a

very prominent thickening, called theostsynaptic density (PSD). In the PSD is an

assortment of some 500 proteins designed to

take the reception of neurotransmitter



Aqueous neurotransmitters are the most commonly encountered means for one neuron to

communicate with another neuron in the mammalian CNS. These water-soluble molecules can

be amino acids, amines or peptides.

Well-defined biochemical steps in each axon terminal produce fusion of neurotransmitter-

filled synaptic vesicles with the membrane of the terminal. A key, initial step to all this is

the invasion of the terminals by an action potential. That depolarization, produced by

opening of voltage-sensitive Na+ channels, leads to opening of a second voltage-sensitive

channel, that for Ca2+. Entry of Ca2+ begins a series of changes in the membrane of synaptic

vesicles and of the presynaptic terminal, leading to fusion of the two. That releases

neurotransmitter into the space between the pre- and post-synaptic membranes - that space

is called the synaptic cleft.

Postsynaptic membranes are sites in which large transmembrane proteins exist in high

concentrations. A large fraction of these transmembrane proteins are designed so that

neurotransmitter molecules attach to them and produce a conformational change when they bind.

These are neurotransmitter receptors. In most excitatory synapses in the mammalian nervous

system, the neurotransmitter receptors are associated with a rich postsynaptic complex to

produce a prominent postsynaptic density or PSD (Figure 22).

You should not think of a synaptic cleft as vacant space. Several varieties of proteins expressed

by pre- and post-synaptic neurons meet in the cleft – usually at the margins of the active zone –

to hold the two synaptic membranes together.

22

Fig 22. This combination

of schematic and electron

micrograph reinforces

the point that for a

chemical synapse

everything is dedicated to

the release and reception

of contents in synaptic

vesicles. Well-regulated

means exist for vesicles

to fuse with the

resynaptic membrane

and release

neurotransmitter into the



Synapses are classified by the elements that form them. Figure 23 illustrates three types of

synapses formed by axons onto different postsynaptic targets – cell bodies (axo-somatic

synapses), dendrites (axo-dendritic synapses) and other axons (axo-axonic synapses).

Fig 23. Axons can form synapses with different targets – these include cell bodies, dendrites

and other axons.

These differences in postsynaptic targets are not trivial. The closer a synapse is to the axon

hillock/initial segment region, the more effective will it be in controlling the generation of actionpotentials. Thus, an axo-somatic synapse is much more likely to produce or suppress action

potentials than is an axo-dendritic synapse. A synapse directly onto an axon (Figure 23) exerts

local control on the release of neurotransmitter (Figure 24), often by regulating the flow of Ca2+

into an axon terminal. The effect produced by such a synapse is called pre-synaptic inhibition.

23



Axons are not the only source of presynaptic elements. In several parts of the CNS, the

dendrites of one cell type are presynaptic and those of another type are postsynaptic. These are

dendro-dendritic synapses. The presynaptic dendrites have all the characteristics of dendrites

AND they possess synaptic vesicles and an appropriate presynaptic membrane for fusion of

those vesicles with the membrane. You should appreciate that dendro-dendritic synapses are away to produce release of neurotransmitter from a neuron even when it does not generate action

potentials.

A difference in the width of the postsynaptic density exists between many excitatory and

inhibitory synapses. Figure 25 documents a difference in synaptic structure detected in the first

electron microscopic studies of the mammalian central nervous system. At a majority of

synapses in the cerebral or cerebellar cortex the postsynaptic density is particularly thick – so

much thicker than the density seen in the presynaptic membrane that the term “asymmetric

synapse” was assigned to them. Other synapses displayed pre- and post-synaptic thickenings of

equal width and so the term “symmetric synapse” was invented to describe them.

Asymmetric synapses are sites of synaptic excitation; symmetric synapses are usually found

where synaptic inhibition is recorded. We have a very good idea why that is true now – it has

everything to do with postsynaptic receptors and their interactions with other proteins.

24

Fig 25. On a dendrite (D) innervated by two axons

terminals are two very different synapses. In the

lower left (red arrow) is a synapse with a thick

ostsynaptic density. Because the PSD is so much

thicker than the presynaptic density this is called an

asymmetric synapse. We know these are synapses

at which the excitatory neurotransmitter, glutamate

is released. In the upper right (green arrow) is a

second synapse with a much less prominent

ostsynaptic density. The thickness of pre- and

ost-synaptic membranes in this second synapse is

so similar we call it a symmetric synapse.

Symmetric synapses are often sites at which the

Fig 24. The release of

neurotransmitter by an axon

terminal can be affected by a

synapse directly onto that

terminal. In this case the effect

of the axo-axonic synapse is

reduce the amount of neurotransmitter released by the

terminal, which leads to a



INTERNAL STRUCTURE OF A NEURON

The Neuronal Cell Body

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. All organelles for transcription, translation, posttranslational processing

and packing of proteins are present in the soma. You will notice that the size of a neuron varieswidely for any one part of the nervous system. In general the variation in size of somata across

the nervous system is correlated with the length and diameter of axons and with the number of

axon terminals given off. That makes sense – if more than 9/10ths of a neuron’s cytoplasm and

membrane is in its axon, supporting and maintaining those elements is the key to health.

1) Nucleus. The soma of every neuron contains its nucleus (Figure 28). Neuronal nuclei contain

large amounts of heterochromatin, most likely a reflection of the fact that beyond a restricted

period in development, a typical neuron leaves mitosis and divides never again.

2) Ribosomes. Neuronal somata 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.

25



a) Ribosomes are found in stacks of rough endoplasmic reticulum. These are referred to

as Nissl bodies, named for the one who discovered their presence in neurons. Nissl used

aniline dyes (basic dyes that bind tightly to acidic molecules such as nucleic acids) to stain

brain sections and was able to visualize clumps in the light microscope. These dyes or

Nissl stains also stain the DNA of nuclei in neurons and supporting cells. The electronmicroscopic correlates to Nissl bodies are stacks of rough ER (Figure 28).

b) Free ribosomes are present throughout the soma and in the shafts of dendrites,

particularly at the origin of dendritic spines. Several observations strongly indicate that

proteins highly concentrated in spines are synthesized in ribosomes at the base of the spine

neck.

26

Fig 28. An anatomically correct drawing of a

neuron illustrates the many organelles in its cellbody. Notice the heterochromatin in the

nucleus and the well-developed rough ER and

Golgi complex. The patches of rough ER seen

in an electron micrograph correspond to Nissl

bodies seen in the light microscope. Small

clusters of free ribosomes, called rosettes, are

present throughout the cytoplasm of the cell

body and dendrites but they and rough ER are

excluded from the axon.

Cytoskeletal elements include microtubules –

you can see them form bundles in the axon

hillock – and intermediate filaments. All cells

derived from an embryonic layer called

ectoderm posses intermediate filaments. Those

in neurons are referred to as neurofilaments.

Mitochondria are present in the cytoplasmeverywhere in a neuron. That tells you neurons



3) Golgi complex. 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.

4) Mitochondria. Neurons consume a lot of energy just keeping the correct ion concentrationsacross the membrane. A major player in that process is a Na+ /K+-ATPase. 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

When you look at a neuron and see its complex shape – dendrites and axons and all that – and

then realize protein synthesis occurs principally in the cell body you can figure out a couple of

things:

1) Something has to establish and maintain the complex shape of a neuron . Dendrites and

axons and spines...all the features that allow one neuron to communicate selectively with

populations of other neurons...require a skeleton, just are your arms and legs and digits require a

skeleton. The neuronal cytoskeleton is a dynamic structure that adapts throughout life to the

changing neuronal environment, so the things that make up the cytoskeleton have to be plastic.

2) If the great mass of proteins is made in the cell body, something has to ship that mass to the

tips of the dendrites and, in particular, to the tips of the axon. The neuronal cytoskeleton isthe structural element for transport of proteins and organelles from the soma to the tips of axons

and dendrites (Figure 29).

27

Fig 29. 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



The role of the cytoskeleton in establishing and maintaining neuronal shape

Microtubules are the primary determinant of neuronal morphology. These are composed of α

and β tubulin and of microtubule associated proteins (MAPs) that differ in size and distribution

along the neuron.

28



2) Neurofilaments are responsible for setting the diameter of an axon. Neurofilaments are

neuronal intermediate filaments, composed of three proteins of differing weights. 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 the axon.

The role of cytoskeleton in axoplasmic transport

To supply the axon and distal parts of the dendrite with proteins, membranes and mitochondria,

an active mechanism of axoplasmic transport moves vesicles and other organelles from the

soma to the tips of the neuron. This is anterograde transport. A similar mechanism, called

retrograde transport, moves worn out organelles and patches of membrane back to the soma

for degradation by lysosomes (Figure 31).

29

Fig 30. An electron micrograph of an axon cut in

cross-section shows the presence of microtubules

(the elements with an obvious lumen) and bundles

of neurofilaments (arrows).

Microtubules are present everywhere in a neuron

except axon terminals and dendritic spines. They

are the highways along which proteins are shipped

from the cell body down the axons and dendrites of

a neuron.

Neurofilaments can be found in dendrites and cell

bodies but they form conspicuous bundles only in

axons.



retrograde transport – by cytoplasmic dynein. Signal proteins in the membranes of these

vesicles determine whether they will attach to kinesin or dynein.

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 the number of glia cells in the CNS

than there are neurons. The folks who first said there was this huge difference made up that ratio

so far as I can tell, and those who have repeated it have done so without performing the single,

basic and most important function of a scientist, which is to ask the questions, who says so and is

it true? Turns out it is dead 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 CNS as a whole the 86 billion neurons

outnumber the 85 billion glial cells.

Those who invented and propagated the 10-to-1 ratio did so to illustrate just how important are

glial cells to the workings of the brain and spinal cord. That they were all wrong by an order of

magnitude does not mean glia are 1/10th so important as these folks had imagined. Glia, as a

group, are essential. Each of the three types of glia has its own structure, chemistry and

function. Together glia are by far the most important means to protect neurons, keep them safe

and warm and happy, and provide them with the means to move messages quickly from cellbody to axon terminals.

31



Oligodendrocytes construct myelin in the CNS. We saw earlier that the difference between

membrane resistance and internal resistance determined how efficiently ions made it down an

axon rather than leak out of it. And we talked about how changes in the diameter of a dendrite

or axon produce changes in internal resistance. Membrane resistance, on the other hand, was

barely mentioned because when left on its own, the plasma membrane changes very little fromone cell to another, much less from one place on a cell to another place on that same cell.

Membrane resistance should stay the same. That is where oligodendrocytes come in.

Oligodendrocyes give rise to a few main processes. Each process divides several times so that

something close to fifty terminal branches come off a single oligodendrocyte (Figure 34). Those

terminal branches repeatedly wrap themselves around a segment of spinal cord, as illustrated

schematically in Figure 34.

32

Fig 33. Electron micrographs of the developing rat

cerebral cortex show individual oligodendrocytes

forming the myelin sheaths around several axons.

Most estimates indicate individual oligodendrocytes

are capable of providing myelin to as many as 50axons. The myelin forms as the repeated wrapping of

an oligodendrocyte arm around an axon segment. This

leaves behind a lipid-rich insulation.

Fig 34. The arms of an

oligodendrocyte wrap themselves

around short segments of many,

nearby axons. The length of themyelinated 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

called nodes of Ranvier.



As the arms of an oligodendrocyte wrap around a myelinated segment, excess cytoplasm is

squeezed out as is the extracellular fluid between each wrapping. The result is a lipid-rich

material – myelin - that works in large part by increasing membrane resistance.

Myelin in the peripheral nervous system is not made by oligodendrocytes. A separate class

of supporting cell, called a Schwann cell, performs that function. And unlike oligodendrocytes,

which provide myelin to segments of many axons, Schwann cells myelinate one segment of one

axon.

A detailed view of myelin shows it to be alternating thin dark lines and wider, paler stripes. The

dark lines, called major dense lines, are phospholipid-rich whereas the paler stripes, the

interperiod lines, are glycolipid rich (Figure 35). Major dense lines are where the two

protoplasmic faces of oligodendrocyte membrane come together as the cytoplasm of the

oligodendrocyte gets squeezed out. Interperiod lines are where two external faces of the

membrane come together as the extracellular fluid between two successive loops of the

oligodendrocyte get squeezed out.

33



Two types of chemical magic are needed to keep myelin sheaths nicely held together (Figure

36). First of all the two external faces have to stick to another – that’s obvious enough. But

secondly, the two protoplasmic faces require some help. Lining them is a high density of

negatively charged proteins that would repel one another unless a positively charged (basic)

material worked to buffer those charges. In the CNS, separate molecules perform the two

functions. Myelin basic protein is cytoplasmic and buffers the negative charges of the

membrane proteins whereas PLP is a glycoprotein that binds homophilically (one PLP in one

membrane binds to a second PLP in a second membrane) to glue together two external faces of

34

Major Dense Line

Interperiod Line

Axon

Fig 35. Each layer of myelin

adds additional resistance to the

low of current out of the axon –

it raises membrane resistance.

Thicker myelin sheaths get

translated, therefore, into faster

conducting action potentials. As

myelin forms, oligodendrocyte

cytoplasm is squeezed out and

two protoplasmic (P) faces of

membrane fuse. Major dense

lines are created where the

hospholipid-rich P faces to

oligodendrocyte membrane come

together. At the same time,

extracellular fluid also gets

squeezed out and external (E)

aces of oligodendrocyte

membrane fuse. Interperiod lines

are created where the

glycoprotein-rich E faces of



the oligodendrocyte membrane. Unlike CNS myelin, PNS myelin contains a multi-functional

protein, called P0, that serves both functions. This transmembrane protein has a positively-

charged, cytoplasmic tail that buffers negative charges and a sugar-rich extracellular region that

binds to other P0 molecules. This difference in myelin chemistry explains why an autoimmune

attack on CNS myelin (multiple sclerosis) produces no effect on PNS myelin.

Astrocytes maintain the environment of the CNS. These star-shaped supporting cells give

rise to processes – lots of them – that occupy the space between neurons. One major target of

astrocyte processes is the surface of brain capillaries (Figure 37).

35

Fig 36. Myelin of both the CNS

and the PNS has a major dense

line, in which a basic protein

buffers the negative charges of

membrane proteins, and an

interperiod line, where a

glycoprotein glues together the

membrane. In CNS myelin,separate proteins perform the two

unctions. In PNS myelin, P0



The intimate relationship between astrocytes and brain capillaries lead early workers to suggest

these supporting cells and their end-feet are the anatomical basis of the blood-brain barrier. That

turns out to be close but no cigar. Brain capillaries are unusual because they have no windows

through which large molecules and even leucocytes can migrate into tissue. Those fenestrations

are eliminated in brain capillaries by a process known, aptly enough, as defenestration (Figure

38). Endothelial cells lining brain capillaries form tight junctions with one another that allowonly small molecules (ions, amino acids and sugars) to reach neurons.

36

Fig 37. Astrocytes give off long,

branching processes that terminate as

astrocytic end-feet. Many end-feet attach

themselves to the surfaces of brain

capillaries (arrows). As a result, morethan 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

in the blood supply.

Astrocytic processes also form a rich

plexus around the cell bodies, axons and

dendrites of neurons. One estimatesuggests astrocytes and their processes



A major function of astrocytes is control of the [K+] around neurons. Astrocytes have plasma

membranes permeable only to K+ and so as the concentration of that ion increases in

extracellular fluid astrocytes will work to remove the excess ions. Gap junctions between

astrocytes provide a mechanism for these ions to flow away from a site of high extracellular

concentration.

Microglia are immune-competent cells of the CNS. Unlike oligodendrocytes and

oligodendrocytes, which are formed from the same embryological precursor cells as neurons,

microglia are derived from blood precursors. They resemble resting macrophages in normal

brain and undergo the same activating events as blood-borne macrophages. When activated they

are to digest damaged and dead cells (Figure 39).

Fig 38. An electron micrograph of a brain capillary

shows the presence of tight junctions between

adjacent endothelial cells (arrows). These junctions

permit only small molecules, less than 1000 daltons

in size, to enter brain tissue. Stars indicate the end- feet of astrocytes.

Circulating factors released by astrocytes inform

capillary endothelial cells to defenestrate. Even

capillaries from muscle defenestrate when cultered

with astroctyes. So astrocytes play an instructive

role in the formation of the blood-brain barrier even

though the tight junctions between endothelial cells

Fig 39. An electron

micrograph of a

microglial cell (left)

shows it consuming a

degenerating cell.

Microglial express the

same MHC proteins as

blood-borne

macrophages (right).

lecture01_neuronstructure-1(1)

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