Unit II: Neurons and
potential: A self-propagating electrochemical impulse. The chain reaction of events
that involves the temporary loss or reversal of polarization at a segment of
the axon and initiates the same repeating sequence of events in the immediately
adjacent portion of the axon ultimately resulting in neurotransmitter release
form the nerve terminal.
and terminal: The transmitting neurofilaments of neurons. Electrochemical
impulses called action potentials travel down the axon resulting in the release
of neurotransmitters from the terminal area where they are stored in discrete
packages called vesicles. The axon terminals are small knob-like swellings
sometimes referred to as boutons from the French for "button." The
terminal is synonymous with the presynaptic membrane.
The receptive neurofilaments of neurons containing receptors where
neurotransmitters bind. Also referred to as the postsynaptic membrane.
Excitatory postsynaptic potential. A depolarizing stimulus that increases the
likelihood that the receiving neuron will "fire" or initiate an
That portion of the brain that appears gray. The color reflects the absence of
myelination (which makes the tissue appear white). The gray matter consists of
the cell bodies, dendrites, and unmyelinated axons that comprise the nervous
Inhibitory postsynaptic potential. A stimulus that decreases the likelihood
that the receiving neuron will fire, usually by hyperpolarizing it.
Fine threadlike structures called dendrites and axons that are special adaptations
and unique features of neurons that enable them to send and receive
Literally "nerve glue." The central nervous system consists of
neurons and glial cells. Neurons constitue about half the volume of the CNS and
glial cells make up the rest. Neurons transmit information, but glial cells do
not. Glial cells provide support and protection for neurons (physically and
nutritionally). They are thus known as the "supporting cells" of the
nervous system. The four main functions of glial cells are: to surround neurons
and hold them in place, to supply nutrients and oxygen to neurons, to insulate
one neuron from another, and to destroy and remove the carcasses of dead
neurons (clean up). The three types of CNS supporting cells are 1) astrocytes,
which are relatively large, star-shaped cells that connect neurons with the
brain's blood supply and also anchor neurons in place; 2) Oligodendrocytes
(oligodendroglia) which function principally to encase axons in insulating
sheaths called myelin which increases the rate at which they can conduct
impulses and 3) Microglia, which help clean up CNS debris. Microglia protect
the brain from invading microorganisms and are thought to be similar in nature
to microphages in the blood system. The supporting cells of the PNS are known
as Schwann Cells.
A nerve cell that receives, integrates and transmits electrochemical signals;
the functional units of the nervous system.
A chemical messenger that carries information from one neuron to another at the
synapse. (Actually, auto-transmission can also occur. This is when a single
neuron synapses with itself.) There are three general categories of
neurotransmitters: (1) monoamines like serotonin, norepinephrine, dopamine, and
acetylcholine (the term amine simply refers to any organic molecule containing
a nitrogen atom derived from ammonia NH3); (2) amino acids like GABA and
glutamate; and (3) neuropeptides or small proteins like beta-endorphin and
The state of having opposite qualities or powers. The difference in
electrochemical charge that develops between the outside and inside of the
neural membrane such that the interior is negatively charged relative to the
exterior. For all intents and purposes, polarization is synonymous with a
neuron's resting membrane potential (e.g., it is not firing).
Specialized molecular binding sites where neurotransmitters dock thereby
producing physiologic effects. Most receptors are large proteins that span the
neural membrane thus having portions on the exterior of the cell where the
neurotransmitters bind, and portions in the cell's interior that subsequently
initiate biochemical reactions within the neuron.
potential: The difference in voltage across a neuronal membrane when the neuron
is not firing.
A mechanism by which a neurotransmitter is pumped or vacuumed back into the
presynaptic terminal that released it.
cell body containing the nucleus and many other cytoplasmic organelles (little
organs of the cell) and the point of origin of the neurofilaments, the
dendrites and axon.
The junction between neurons transmitting and receiving membranes. Usually a
physical gap across which neurotransmitters diffuse when released.
Threshold of excitation. A critical degree of excitation or depolarization at
which the neuron initiates an action potential or fires in an all-or-none
matter: Whitish appearing patches and paths in the brain composed of myelinated
Neural Transmission: The
Language of Chemical Communication
also referred to as nerve cells, are the functional units of the nervous
system. Essentially, neurons receive, integrate, and transmit electrochemical
impulses via neurotransmitter-dependent, ionic and/or enzymatic interactions
across cellular membranes. Like all nucleated animal cells (i.e., cells having
a nucleus or eukaryotes) neurons have the typical complement of organelles, but
have in addition some unique features that make them especially well adapted to
their roles as signal senders and receivers. These unique characteristics are
neurofilaments called dendrites and axons.
it is a slight oversimplification, dendrites can be thought of as the neuron's
receptive membrane or the site where most incoming messages are received. A
given neuron can have many points on its soma where dendrites originate. Axons,
the neuron's transmitting components, are the structures that send signals.
While both dendrites and axons may branch out into numerous offshoots, usually
the axon originates from a single trunk called the axon hillock where it leaves
the cell body. Most neurons synthesize their neurotransmitters in their cell
bodies, package them in membranous sacks called vesicles (which protect the
neurotransmitter from enzymatic degradation), and store them in their axon
terminals where they await release upon the arrival of an action potential in
order to be released. Neurons that release monoamine neurotransmitters also
have the capacity of synthesizing neurotransmitters at the presynaptic
neuron is at rest (i.e., not "firing" or sending an impulse) a very
narrow margin of the axon's interior is negatively charged. Conversely, a very
narrow margin of the exterior fluid surrounding the outer membrane of the axon
is positively charged. This separation of charge, so that the interior of the
neuron is negatively charged relative to its exterior, is termed polarization
(the state of having opposite qualities or powers). Polarization is due to a
property of the cellular membrane called selective permeability which means
that the membrane allows some molecules to cross into or out of the cell, but
not others. Another important factor that helps to polarize the neuron is an
active (energy-requiring), membrane-bound, molecular pump that extrudes sodium
ions and retrieves potassium ions. Since the pump has binding sites of three
sodium atoms, but only two for potassium atoms, for every three sodium ions
pumped out of the cell, only two potassium ions are taken in. Because the
resting neural membrane is normally impermeable to sodium, a large
concentration gradient develops so that the quantity of sodium ions outside the
neuron is much greater than the quantity of sodium within it. Since substances
tend to seek equilibrium by moving down concentration gradients (i.e.,
molecules will randomly move by diffusion from areas of high concentration to
areas of lower concentration) a significant tension builds, tending to force
the sodium into the cell. Similarly, inside the cell's axon a concentration
gradient develops that favors the movement of potassium ions out of the neuron.
The net result is that the immediate interior of the neuron is negatively
charged relative to the immediate exterior. This charge difference, of about 70
millivolts, is called the neuron's resting membrane potential and can be
thought of as analogous to a cocked crossbow.
the TOE is exceeded, the crossbow will fire by suddenly releasing the energy
stored in its bow. Similarly, since the sodium and potassium ions are seeking
to equalize their distribution across the axon's membrane (they are
"cocked") if anything occurs to increase the permeability of the
membrane to them, an immediate rush of sodium into and potassium out of the
cell will result.. This flip-flop of ions - sodium in, potassium out - causes a
change in the neuron's polarity so that its interior becomes momentarily positive
relative to its exterior, and the neuron is said to have depolarized.
neurotransmitter-receptor interactions increase membrane permeability to sodium
ions which produces a decrease in the degree of polarization (partial
depolarization) because the interior membrane margin becomes less negatively
charged due to the influx of positively charged sodium ions. This is referred
to as an EPSP, or excitatory postsynaptic potential, and tends to push the
neuron toward firing. Other neurotransmitter-receptor interactions produce an
increase in the degree of polarization (hyperpolarization) either because of
increasing membrane permeability to negative ions like chloride, thus adding
additional negative molecules to the already negative intracellular environment,
or by further decreasing permeability to positive ions (so that even more
accumulate outside the membrane). This is called an IPSP, or inhibitory
postsynaptic potential, which tends to inhibit the neuron from firing.
moment, a neuron can be receiving dozens, perhaps even hundreds or thousands,
of signals from many other neurons. Some can be EPSPs while others might be
IPSPs. When the amount of excitation from EPSPs crosses a threshold, the
threshold of excitation or TOE, the neuron fires. The process works as follows.
In a nerve cell that is "at rest," positively charged Na+ (sodium)
ions are kept outside the cell, whereas positively charged K+ (potassium) and
negatively charged Cl- (chlorine) ions can pass into the cell. Thus the environment
inside the cell is electrically more negative than the environment outside the
cell. In this polarized state the cell has potential energy that can be
released by a stimulus to the cell membrane.
that is of sufficient intensity causes sodium gates in the membrane to open,
allowing positively charged Na+ ions to rush into the cell. This causes a
reverse in the cell's electrical polarity, so that the environment inside the
cell now is more positive than the environment outside the cell. After the cell
reaches its maximally positive state, its sodium gates close and its potassium
gates open to allow the positively charged potassium ions (K+) to leave the
cell. The environment inside the cell once again becomes more negative than the
environment outside the cell. At this point, the sodium-potassium pump removes
sodium ions and retrieves potassium ions thus restoring the membrane's resting
potential. This complete sequence of events is termed the action potential and
is initiated at the axon hillock; the conical area of origin of the axon from
the nerve cell body.
occurrence of the action potential at any given point along the axon triggers a
similar succession of changes in the immediately adjacent portion of the axon.
And as the sequence is replicated there, a similar series of events arises in
the next axonal segment and so on down the line. In this manner, the action
potential is self-propagated like a wave along the entire length of the axon.
Most neurons, however, have myelin sheaths covering most of their axons like
insulation around an electric cord. The myelin sheaths surrounding axons have
discrete segments called nodes where the axon's membrane is unsheathed. This
allows the action potential to jump from node to node, rather than traversing
along the entire length of the axon, thus increasing the speed that nerve
signals can travel. For example, some large myelinated nerve fibers, such as
those supplying skeletal muscles, conduct impulses as fast as 120 meters per
second (360 miles per hour), compared with speeds of only a few millimeters per
second (2 miles per hour) in small, unmyelinated fibers like those supplying
the digestive tract. Note that the process within the neuron axon involves
the action potential reaches the terminal portions of the axon, a cascade of
events takes place that results in the release of neurotransmitters into the
synaptic space - a process called exocytosis. Basically, when the action
potential reaches the terminal button, calcium channels are opened. As calcium
flows into the presyntaptic neuron, it anchors the vesicles holding the
neurotransmitters onto the membrane so that the chemicals can be released onto
the synapse. Note that communication between neurons involves a chemical
process. Once released the neurotransmitter diffuses across the synapse where
some of it binds to specific molecular receptors on the postsynaptic membrane.
Depending on the type of neurotransmitter and the nature of the receptor, the
neurotransmitter-receptor interaction will produce either an EPSP or an IPSP.
When the sum of the EPSPs and IPSPs exceeds the TOE, the postsynaptic neuron
will fire. This entire process is called neural transmission and the
communication between neurons is called the first messenger system.
addition to regulating ion channels in the cellular membrane, many
neurotransmitter-receptor interactions activate second-messenger systems.
Briefly, the second-messenger systems involve complex biological reactions that
take place in the cell's interior. The neurotransmitter as the first messenger
activates or inhibits other chemicals inside the cell that then also function
as chemical messengers. These second-messengers, in turn, initiate a variety of
physiologic events, usually involving activation of specific enzymes, that
produce additional (third) chemical messengers and biochemical reactions that
can ultimately influence the genetic functions of the cell. It is through these
second-messenger mediated intracellular process that most psychotropic
medications are believed to exert their therapeutic effects.
there are three major types of neurotransmitters that can be classified
according to their chemical composition or molecular structure: the monoamines,
amino acids, and neuropeptides. A commonly asked question is if a given
neurotransmitter is excitatory or inhibitory. The answer is "it
depends." While some transmitters are typically described as inhibitory
(e.g., GABA) and others as excitatory (e.g., norepinephrine), whether or not a
given neurotransmitter produces an IPSP or an EPSP depends on the receptor it
binds to. Most transmitters bind to several subtypes of receptors, not just
one. For example, there are at least seven varieties of serotonin receptors,
five kinds of dopamine receptors, and at least 3 receptors for norepinephrine.
At some receptors.† norepinephrine
is excitatory (e.g., at most of its targets in the sympathetic nervous system)
while at others it is inhibitory (e.g., at alpha-2 receptors in the locus
ceruleus, a brain stem structure implicated in acute anxiety and panic). Thus,
there are probably no absolutely excitatory nor invariably inhibitory
neurotransmitters. Postsynaptic potentials always depend on the specific
transmitter-receptor interaction. Furthermore, many neurotransmitters are found
all through the body, not only in the CNS, and play many different roles at
these peripheral locations (e.g., serotonin is widely distributed throughout
the gut and on the surface of red blood cells).
neurotransmission is very fast in onset (within millseconds). For example, two
fast-onset neurotransmitters are GABA (which is primarily inhibitory), and
Glutamate, which is primarily an excitatory neurotransmitter. Some
neurotransmitters are slow acting (up to two seconds after binding at the
post-receptor site). These include some of the monamine neurotransmitters and
some of the neuropeptides. These slow acting NT are sometimes referred to as
neuromodulators because they can influence the effects of future
neurotransmissions at the same post-synaptic site(s). In some cases, these
effects can last for a few days.
most well known small molecule neurotransmitters are the monoamines which consist
of a variety of chemicals including serotonin, norepinephrine, epinephrine,
dopamine, acetylcholine, and histamine. Serotonin has many important functions
in the CNS and is thought by some to be the "work horse" of
neurotransmitters. It is involved in sleep, arousal, motivation, appetite, and
sex. Norepinephrine plays a "Paul Revere" role in the brain in that
it sounds the alarms that mobilize our fight-or-flight stress response. Both
serotonin and norepinephrine appear to be involved in depressive illnesses.
Norepinephrine's chemical cousin, epinephrine, is not well understood as a
neurotransmitter, but it appears to be involved in regulating some autonomic
(life support) processes. Dopamine is critically important in mediating
extrapyramidal motor control and when deficient results in symptoms of
Parkinson's disease. It is also involved in regulating the release of some
important pituitary hormones, and is clearly related to psychotic disorders
like schizophrenia, some drug addictions, and the brainís reward system.† Acetylcholine's role in the CNS seems
related to learning and memory. Alzheimer's disease, a progressive
neurodegenerative illness whose hallmark is memory loss, appears to involve the
degeneration of the brains major acetylcholine producing structure, the
hippocampus. Histamine's function in the brain is not well understood.
amino acid neurotransmitters that have been extensively studied are the
predominantly inhibitory transmitters GABA (gamma-aminobutyric acid) and
glycine; and glutamate and aspartate which both appear to be predominantly
excitatory. In addition to monoamines and amino acids, the brain contains an
unknown number of peptide (small protein) neurotransmitters called
neuropeptides. Two of the most well studied neuropeptides are beta-endorphin,
which is a naturally occurring opiate-like molecule, and substance P which
appears to be important in conveying pain sensations and is now under
investigation for it's suspected role in depression. Many of the peptide
transmitters are believed to act as neuromodulators or neuroregulators by
modulating or regulating the binding of other transmitters like the monoamines
and amino acids at their receptors. They are also thought to exert longer
lasting postsynaptic influences than monoamine and amino acid transmitters.
the most well studied neurotransmitters are the monoamine transmitters,
especially acetylcholine and norepinephrine since they occur in high
concentrations in the peripheral nervous system and are, therefore, more
accessible and more easily segregated than centrally located transmitters. The
monoamines collectively account for only 5 to 10 percent of the synapses in the
human brain whereas the amino acid transmitters account for up to 60 percent of
CNS synapses. While only a handful of neurotransmitters have been confidently
classified to date, it is believed that as many as several hundred yet to be
identified neurotransmitters exist. To make matters still more complex, it is
now know that most neurons have co-localized neurotransmitters (that is, a
single neuron may produce and release more than one neurotransmitter). In fact,
it appears that a given neuron can release as many as three different
neurotransmitters simultaneously; usually one of each of the three major types
- a monoamine along with an amino acid and a neuropeptide.
complicate things even further, there are numerous permutations of synaptic
connections (Hyman & Nestler, 1993). Most synapses are axodendritic, i.e.,
the axon of one neuron synapses with the dendrite of another. But there are
also axosomatic (axon to cell body), and axoaxonic (one neuron's axon synapses
with another neuron's axon) synapses. In addition, dendrites may also synapse
with each other in dendro-dendritic connections. And to introduce yet another
layer of complexity, not all neurons communicate at chemical synapses. Some
neurons interconnect at what are described as electrical synapses.
in and of themselves are not especially smart. As we have described, they can
do very few things, such as fire or not fire, and communicate with a relatively
limited vocabulary of only a few types of chemicals. But, put one hundred
billion of them together in a small area, and let each one "speak"
with thousands of other neurons in very specific and precise ways, and a
literal brainstorm of activity will take place resulting in the infinite
diversity of human conscious experience.
Brief Description of the Action
have discussed, neurons send messages through an electrochemical process.
Chemicals in the body that have an electrical charge are called
"ions." The important ions in the nervous system are sodium and
potassium (both have 1 positive charge, +), calcium (has 2 positive charges,
++) and chloride (has a negative charge, -). There are also some negatively
charged protein molecules inside of the cell. Recall that nerve cells are
surrounded by a membrane that allows some ions to pass through and which also
blocks the passage of other ions. This type of membrane is called
neuron is not sending a signal, it is said to be "at rest." When a
neuron is at rest, the inside of the neuron is negatively charged relative to the
outside. If you measure the difference in the voltage between the inside and
outside of the neuron, you have the resting potential. The resting membrane
potential of a neuron is about -70 mV (mV=millivolt) - this means that the
inside of the neuron is 70 mV less than the outside.
that the measurement of voltage is always relative - comparing two regions to
each other. If one compares the region with more positive charges to a region
with more negative charges one has a positive voltage. If you compare a region
with more negative charges to a region with more positive charges, the voltage
is negative. Thus in the axon, there are more negative charges on the inside
than on the outside during the resting potential, giving the axon a negative
voltage when comparing the inside to the outside
the concentrations of the different ions attempt to balance out on both sides
of the membrane, they cannot because the cell membrane allows only some ions to
pass through channels (ion channels). At rest, potassium ions (K+) can cross
through the membrane easily, but (at rest,) chloride ions (Cl-) and sodium ions
(Na+) have a more difficult time crossing. The negatively charged protein
molecules inside the neuron cannot cross the membrane.
addition to these selective ion channels, there is a pump that uses energy to
move 3 sodium ions out of the neuron for every 2 potassium ions it puts in.
(the sodium/potassium ATPase). This activity results in a net loss of positive
charges within the cell. In addition, some potassium channels in the plasma
membrane are "leaky" allowing a slow diffusion of K+ out of the cell
(which also results in a net loss of positive charges). At rest, the
concentration of Na+ outside the cell is about10 times greater than that inside
the cell. Also, the concentration of K+ inside the cell is about 20 times
greater than that outside the cell.
resting potential indicates what is happening with the neuron at rest. The
action potential indicates what happens when the neuron transmits information
down an axon, away from the cell body, and fires. Neuroscientists use other
words, such as a "spike" or an "impulse" to describe the
action potential. The action potential is an explosion of electrical activity
that is created by a depolarizing current. This means that some event (a
stimulus) causes the resting potential to move toward 0 mV. When the
depolarization reaches about -55 mV a neuron will fire an action potential.
This is the threshold of excitation (TOE). If the neuron does not reach this
critical threshold level, then no action potential will fire. However, when the
TOE level is reached, an action potential of a fixed sized will always fire. In
any given neuron, the size of the action potential is always the same. There
are no big or small action potentials and all action potentials are the same
size. Therefore, the neuron either does not reach the threshold or a complete
action potential is fired - this is the "ALL OR NONE" principle.
"cause" of the action potential is an exchange of ions across the
neuron membrane. A stimulus first results in the opening of sodium channels.
Because there are a lot more sodium ions on the outside, and the inside of the
neuron is negative relative to the outside (opposite charges attract each
other), sodium ions rush into the neuron. Sodium has a positive charge, so the
neuron becomes momentarily more positive (on the inside) and becomes
depolarized. The sudden complete depolarization of the membrane opens up more
of the voltage-gated sodium channels in adjacent portions of the membrane. In
this way, a wave of depolarization sweeps along the cell. This is the action
potential, which is also called the nerve impulse. In myelinated neurons , the
action potenial jumps from unmyelinated node to node in order to speed up
transmission. The voltage-gated sodium channels of myelinated neurons are
confined to these spots (called nodes of Ranvier).
the inside of the axon becomes sufficiently positive, about 30 mV is given as
an average value, the sodium channels close. In addition to the sodium channels
closing, the potassium (K+) channels open, but it takes longer for potassium
channels to open. When they do open, potassium rushes out of the cell,
reversing the depolarization.. This causes the action potential to go back
toward -70 mV (a repolarization). The action potential actually goes past -70
mV (a hyperpolarization) because the potassium channels stay open a bit too
long. Gradually, the ion concentrations go back to resting levels and the cell
returns to -70 mV. Until the 70 mv polarity is reestablished, the neuron will
not be able to fire again. This is called the refractory period and lasts about
,.001 seconds. However, on the average, an excited neuron can fire about 500 to
1000 times in one second.
neurotransmitters inhibit the transmission of nerve impulses (IPSP). They do
this by opening
chloride channels (letting negatively-charged chloride ions (Cl-) IN and
potassium channels in the plasma membrane (positively-charged potassium ions
the threshold voltage of the cell is unchanged, it now requires a stronger
excitatory stimulus to reach threshold.
example, gamma amino butyric acid (GABA). This neurotransmitter inhibits nerve
transmission by both mechanisms:
binding to GABAA receptors opens chloride channels in the neuron.
binding to GABAB receptors opens potassium channels.
of the axon hillock
single neuron may have thousands of other neurons synapsing on it. Some of these
release activating (depolarizing) neurotransmitters; others release inhibitory
(hyperpolarizing) neurotransmitters. The receiving cell is able to integrate
EPSP created by a single excitatory synapse is insufficient to reach the
threshold of the neuron.
EPSPs created in quick succession, however, add together
("summation"). If they reach threshold, an action potential is
EPSPs created by separate excitatory synapses can also be added together to reach
Activation of inhibitory synapses makes the resting potential of the neuron
more negative. The resulting IPSP may prevent what would otherwise have been
effective EPSPs from triggering an action potential.
action potential is usually generated in the axon hillock. Having neither
excitatory nor inhibitory synapses of its own, it is able to evaluate the total
picture of EPSPs and IPSPs created in the dendrites and cell body.
if, over a brief interval, the sum of depolarizing signals minus the sum of the
hyperpolarizing signals exceeds the threshold of the axon hillock will an
action potential be generated. In most neurons, this process occurs very
rapidly (e.g., under a second).