• An animal’s ability to survive and to maintain homeostasis depends largely on how effectively it

detects and responds to stimuli, the changes that take place in its environment.
• The nervous system is composed mainly of two specialized types of cells: neurons and glial cells.
• The nervous system is the principal regulatory system in animals. Regulation requires
communication, and the nervous system transmits information to and from all parts of the
body.
• Neurobiology is one of the most exciting areas of biological research. Active areas of research
include neurotransmitters, the chemical messengers used by neurons to signal other neurons,
and the receptors that bind with the neurotransmitters.
• Neurogenesis, the production of new neurons, has been a very interesting focus of research.

41.1Neural Signaling: An Overview

• Survival depends on identifying and evaluating these stimuli, and then responding effectively.
• In most animals, responses to stimuli depend on neural signaling, the transmission of
information by neurons, conducting cells of the nervous system.
• Neural signaling typically involves four processes: reception, transmission, integration, and the
action by effectors (muscles or glands) that brings about the actual response.
➢ Reception, the process of detecting a stimulus, is the job of neurons and of
specialized sensory receptors such as those in the skin, eyes, and ears.
➢ Neural transmission is the process of sending messages along a neuron, from one
neuron to another, or from a neuron to a muscle or gland.
o In vertebrates a neural message is transmitted from a receptor to the central
nervous system (CNS), which consists of the brain and spinal cord.
➢ Integration involves sorting and interpreting incoming sensory information and
determining the appropriate response.
• Neurons that transmit information to the CNS are called afferent neurons (meaning “to carry
toward”); they are also called sensory neurons.
• Afferent neurons generally transmit information to interneurons, also known as association
neurons, in the CNS. Most neurons, perhaps 99% of them, are interneurons. Their function is
to integrate input and output.
➢ Integration involves sorting and interpreting incoming sensory information and
determining the appropriate response.
• Efferent neurons (meaning “to carry away”) transmit neural messages from the CNS
to effectors (muscles and glands).
• Efferent neurons that signal skeletal muscle are called motor neurons. The action by
effectors brings about the actual response to the stimulus.
• Sensory receptors and afferent and efferent neurons are part of the peripheral nervous system
(PNS).
• In summary, information flows through the nervous system in the following sequence:

reception by sensory receptor ➝ transmission by afferent neuron ➝ integration by interneurons in CNS

➝ transmission by efferent neuron ➝ action by effectors ➝ actual response
41.2Neurons and Glial Cells
• Neurons are specialized to receive and send information.
• Glial cells support and protect neurons and carry out many regulatory functions.

Neurons Receive Stimuli and Transmit Neural Signals

• The neuron is highly specialized to receive and transmit information. Neurons produce and
transmit electrical signals called nerve impulses, or action potentials. The neuron is
distinguished from other cells by its long processes (cytoplasmic extensions).
• The largest portion of the neuron, the cell body, contains the bulk of the cytoplasm, the nucleus,
and most of the other organelles. Typically, two types of processes project from the cell body of
a multipolar neuron.
• Numerous dendrites extend from one end, and a long, single axon projects from the opposite
end. Dendrites are typically short, highly branched processes specialized to receive stimuli and
send signals to the cell body. The cell body integrates incoming signals.
➢ Although microscopic in diameter, an axon may be 1 m or more in length and may
divide, forming branches called axon collaterals. The axon conducts nerve impulses
away from the cell body to another neuron or to a muscle or gland.
• At its end the axon divides, forming many terminal branches that end in synaptic terminals, also
called axon terminals.
➢ The synaptic terminals release neurotransmitters, chemicals that transmit signals from
one neuron to another or from a neuron to an effector.
➢ The junction between a synaptic terminal and another neuron (or effector) is called
a synapse. Typically, a small space exists between these two neurons. Neurons
communicate with one another at synapses.
• In vertebrates the axons of many neurons outside the CNS are surrounded by a series
of Schwann cells.
 • The plasma membranes of these glial cells contain myelin, a white, fatty material.
➢ Schwann cells wrap their plasma membranes around the axon, forming an insulating
covering called the myelin sheath.
➢ Gaps in the myelin sheath, called nodes of Ranvier, occur between successive Schwann
cells. At these points the axon is not insulated with myelin.
➢ Axons more than 2 µm in diameter have myelin sheaths and are described
as myelinated. Those of smaller diameter are generally unmyelinated.

Certain Regions of the CNS Produce New Neurons

• We described Nobel laureate Santiago Ramon y Cajal idea that neurogenesis, the production of
new neurons, does not occur in the CNS after birth. Cajal’s idea was widely accepted for many
years.
• Since the 1970s Fernando Nottebohm has studied birdsong, including its neural basis.
Nottebohm found that birds produce new neurons daily in the brain center that regulates their
songs.
• However, other investigators, notably psychologist Elizabeth Gould have provided additional
data that together have falsified Cajal’s hypothesis.
➢ Gould demonstrated neuron proliferation in primates. She and her research team also
discovered that stress damages the brain and inhibits mitosis in neurons. They stressed
newborn rats by separating them from their mothers for up to 3 hours a day. The
stressed rats did not learn how to cope with stress, and as adults they had fewer new
neurons in certain areas of their brains than control rats.
• Neurobiologists now agree that neurogenesis does occur regularly in the adult mammalian
brain, at least in certain areas of the hippocampus and in the lining of the lateral ventricles.

Axons Aggregate to Form Nerves and Tracts

• A nerve consists of hundreds or even thousands of axons wrapped together in connective tissue.
• Within the CNS, bundles of axons are called tracts or pathways rather than nerves.
• Outside the CNS, a mass of neuron cell bodies is called a ganglion (plural, ganglia).
• Inside the CNS, a collection of cell bodies is called a nucleus, rather than a ganglion.
Glial Cells Play Critical Roles in Neural Function
• Glial cells collectively make up the neuroglia (literally, “nerve glue”). Glial cells were once
thought to be passive cells that simply support and protect the neurons.
➢ More than 75% of the cells in the human CNS are glial cells. They account for only about
50% of the brain volume because they do not branch as extensively as neurons.
• Four types of glial cells are found in the vertebrate CNS: astrocytes, oligodendrocytes,
ependymal cells, and microglia.
➢ Astrocytes, the most numerous glial cells, are star-shaped. These cells provide both
physical support and nutrients for neurons. They help regulate the composition of the
extracellular fluid in the CNS by removing excess potassium ions. This action helps
maintain normal neuron excitability.
o Some astrocytes position the ends of their long processes on blood vessels in
the brain. In response, endothelial cells lining the blood vessels form tight
junctions that prevent many potentially harmful substances in the blood from
entering the brain tissue. This protective wall is the blood–brain barrier.
Astrocytes also help regulate self-cleaning mechanisms in the brain that involve
flushing out wastes with cerebrospinal fluid.
o Neurobiologists have shown that astrocytes are functionally connected
throughout the brain. These interesting glial cells participate in information
signaling by coordinating activity among neurons.
o They communicate through gap junctions and with signaling molecules.
Although astrocytes can generate only weak electrical signals, they
communicate with one another and with neurons by means of chemical signals.
Astrocytes appear to respond to neurotransmitters released by neurons. They
also help regulate the reuptake of excess neurotransmitters from synapses.
Astrocytes induce synapse formation and can strengthen activity of synapses in
the brain. Their actions appear to be important in learning and memory.
o Astrocytes play a role in development by guiding neurons to appropriate
locations in the body. Certain astrocytes function as stem cells in the brain and
spinal cord. These cells can give rise to new neurons, additional astrocytes, and
certain other glial cells. Taken out of their normal environment in the adult
mouse brain, astrocytes can give rise to cells of all germ layers (the embryonic
tissue layers: ectoderm, mesoderm, and endoderm). Human astrocytes may
someday be used to produce specific types of cells needed for treating various
medical conditions.
➢ Oligodendrocytes are glial cells that envelop neurons in the CNS, forming insulating
myelin sheaths around them. Because myelin is an excellent electrical insulator, its
presence speeds transmission of neural impulses.
o In the neurological disease multiple sclerosis, patches of myelin deteriorate at
irregular intervals along axons in the CNS and are replaced by scar tissue. This
damage interferes with conduction of neural impulses, and the victim suffers
loss of coordination, tremor, and partial or complete paralysis of parts of the
body. Multiple sclerosis affects more than 2 million people worldwide.
o Although sometimes considered glial cells, Schwann cells are located outside
the CNS.
➢ Ependymal cells are ciliated glial cells that line the internal cavities of the CNS.
Ependymal cells help produce and circulate the cerebrospinal fluid that bathes the brain
and spinal cord of vertebrates. There is some evidence that ependymal cells function as
neural stem cells, and that they have the potential to give rise to new neurons, as well
as to glial cells.
➢ Microglia are actually specialized macrophages (phagocytic cells that ingest and digest
cell debris and bacteria). Microglia respond to signals from neurons and are important in
 mediating responses to injury or disease. These cells are found near blood vessels.
When the brain is injured or infected, microglia multiply and move to the affected area.
There they remove bacteria and cell debris by phagocytosis. In addition, they release
signaling molecules (also produced by macrophages and certain other cells in the
immune system) that mediate inflammation. Microglia appear to help regulate the
number of neurons in the developing brain by destroying neurons that are not needed.

Type of Glial Cell Functions

ASTROCYTES Physically support neurons
Help transfer nutrients to neurons
Remove excess K + , which helps regulate composition of extracellular
fluid in CNS
Induce blood vessels to form blood–brain barrier and help maintain
the barrier
Communicate with one another and with neurons
Induce synapse formation and strengthen synaptic transmission by
chemically signaling neurons
Respond to neurotransmitters and help regulate neurotransmitter
reuptake
May link receptors in the brain associated with learning and memory
Guide neurons during embryonic development

OLIGODENDROCYTES Form myelin sheaths around neurons in CNS

May be important in learning and memory

EPENDYMAL CELLS Line cavities of CNS

Help produce and circulate cerebrospinal fluid
May function as neural stem cells

MICROGLIA Phagocytosis of bacteria and debris

Release signaling molecules that mediate inflammation
May play important role in regulating the number of neurons in the
developing brain by destroying neurons that are not needed

41.3Transmitting Information along the Neuron

• Most animal cells have a difference in electric charge across the plasma membrane: the electric
charge inside the cell is more negative than the electric charge of the extracellular fluid.
➢ The plasma membrane is said to be electrically polarized, meaning that one side, or
pole, has a different charge than the other side. When electric charges are separated in
this way, a potential energy difference exists across the membrane.
• The difference in electric charge across the plasma membrane gives rise to an electrical
gradient.
• Voltage is the force that causes charged particles to flow between two points. The voltage
measured across the plasma membrane is a form of potential energy called the membrane
potential.
➢ If the charges are permitted to come together, they have the ability to do work. Thus,
the cell can be thought of as a biological battery.
➢ In excitable cells, such as neurons and muscle cells, the membrane potential can change
rapidly. Such changes can transmit signals to other cells.
Ion Channels and Pumps Maintain the Resting Potential of the
Neuron
• The membrane potential in a resting (not excited) neuron or muscle cell is its resting potential.
The resting potential is generally expressed in units called millivolts (mV). (A millivolt equals one
thousandth of a volt.)
➢ Like other cells that can produce electrical signals, the neuron has a resting potential of
about 70 mV. By convention, this value is expressed as −70 mV because the cytosol
close to the plasma membrane is negatively charged relative to the extracellular fluid.
• Biologists can measure the potential across the membrane by placing one electrode inside the
cell and a second electrode outside the cell and connecting them through a very sensitive
voltmeter or oscilloscope.
➢ If you place both electrodes on the outside surface of the neuron, no potential
difference between them is registered. (All points on the same side of the membrane
have the same charge.) However, once one of the electrodes penetrates the cell, the
voltage changes from zero to approximately −70 mV.
• Two main factors determine the magnitude of the membrane potential: (1) differences in the
concentrations between specific ions inside the cell and those in the extracellular fluid and (2)
selective permeability of the plasma membrane to these ions.
➢ The distribution of ions inside neurons and in the extracellular fluid surrounding them is
like that of most other cells in the body. The potassium ion K + concentration is about 10
times greater inside the cell than outside the cell.
➢ In contrast, the sodium ion Na+ concentration is about 10 times greater outside than
inside. This asymmetric distribution of ions across the plasma membrane at rest is
brought about by the action of selective ion channels and ion pumps.
➢ In vertebrate neurons (and skeletal muscle fibers), the resting membrane potential
depends mainly on the diffusion of ions down their concentration gradients.
Ions Cross the Plasma Membrane by Diffusion through Ion
Channels
• Net movement of ions occurs from an area of higher concentration of that type of ion to one of
lower concentration. Membrane proteins form ion channels that typically allow only specific
types of ions to pass.
• Neurons have three types of ion channels: passive ion channels, voltage-activated
channels, and chemically activated ion channels.
➢ Passive ion channels permit the passage of specific ions such as Na+, K + , Cl− ,
and Ca2+.
➢ Unlike voltage-activated and chemically activated ion channels, passive ion channels are
not controlled by gates.
• Potassium channels are the most common type of passive ion channel in the plasma membrane,
and cells are more permeable to potassium than to other ions.
➢ In fact, in the resting neuron, the plasma membrane is up to 100 times more permeable
to K + than to Na+. When pumped out of the neuron, Na+ cannot easily pass back into
the cell.
➢ However, K + pumped into the neuron easily diffuses out.
➢ Potassium ions leak out through passive ion channels following their concentration
gradient. As K + diffuse out of the neuron, they increase the positive charge in the
extracellular fluid relative to the charge inside the cell.
 ➢ The resulting change in the electrical gradient across the membrane influences the flow
of ions. This electrical gradient forces some of the positively charged potassium ions
back into the cell.
➢ The membrane potential at which the flow of K + inward (due to the electrical gradient)
equals the flow of K + outward (because of the concentration gradient) is
the equilibrium potential for K + .
➢ The equilibrium potential for any particular ion is a steady state in which opposing
chemical and electrical flows are equal and there is no net movement of the ion.
o The equilibrium potential for K + in the typical neuron is −90 mV.
o The equilibrium potential for Na+ is +60 mV; it differs from the equilibrium
potential of K + because of the difference in concentration of Na+ across the
membrane (concentration is high outside and low inside the cell).
• Because the membrane is much more permeable to K + than to Na+, the resting potential of the
neuron is closer to the potassium equilibrium potential than to the sodium equilibrium
potential. (Remember that the resting potential of the neuron is about −70 mV.)
➢ The resting potential is primarily established by the net flow of K + into the neuron.
However, the net flow of Na+ outward contributes to the resting potential. Because the
plasma membrane is permeable to negatively charged chloride ions, Cl− also contribute
slightly.
➢ These ions accumulate in the cytosol close to the plasma membrane. Negative charges
on large molecules such as proteins add to the negative charge in the cytosol. These
large anions cannot cross the plasma membrane.

Ion Pumping Maintains the Gradients that Determine the Resting

Potential
• The neuron plasma membrane has very efficient sodium–potassium pumps that actively
transport Na+ out of the cell and K + into the cell.
➢ These pumps require ATP to pump Na+ and K + against their concentration and
electrical gradients.
➢ For every three Na+ pumped out of the cell, two K + are pumped in. Thus, more positive
ions are pumped out than in. The sodium–potassium pumps maintain a higher
concentration of K + inside the cell than outside and a higher concentration
of Na+ outside than inside.
• In summary, the development of the resting potential depends mainly on the diffusion
of K + out of the cell. However, once the neuron reaches a steady state, net Na+ diffusion into
the cell is greater than net K + diffusion out of the cell. This situation is offset by the sodium–
potassium pumps that pump three Na+ out of the cell for every two K + pumped in.

Graded Local Signals Vary in Magnitude

• Neurons are excitable cells. They respond to stimuli and can convert stimuli into nerve impulses.
➢ An electrical, chemical, or mechanical stimulus may alter the resting potential by
increasing the membrane’s permeability to sodium ions.
• When a stimulus causes the membrane potential to become less negative (closer to zero) than
the resting potential, that region of the membrane is depolarized. Because depolarization brings
a neuron closer to transmitting a neural impulse, it is described as excitatory.
➢ In contrast, when the membrane potential becomes more negative than the resting
potential, the membrane is hyperpolarized. Hyperpolarization is inhibitory; it decreases
the neuron’s ability to generate a neural impulse.
 • A stimulus may change the potential in a relatively small region of the plasma membrane. Such
a graded potential is a local response. It functions as a signal only over a very short distance
because it fades out within a few millimeters of its point of origin.
➢ A graded potential varies in magnitude; that is, the potential charge varies depending on
the strength of the stimulus applied. A larger stimulus causes a larger change in
permeability and a greater change in membrane potential.

Axons Transmit Signals Called Action Potentials

• When a stimulus is strong enough, a rapid, large change in membrane potential occurs,
depolarizing the membrane to a critical point known as the threshold level.
➢ At that point, the neuron fires a nerve impulse, or action potential, an electrical signal
that travels rapidly down the axon into the synaptic terminals. All cells can generate
graded potentials, but only neurons, muscle cells, and a few cells of the endocrine and
immune systems can generate action potentials.
• In a series of experiments in the 1940s, pioneering English researchers Alan Hodgkin and
Andrew Huxley inserted electrodes into large axons found in squids.
➢ By measuring voltage changes as they varied ion concentrations, these investigators
showed that passage of Na+ ions into the neuron and K + ions out of the neuron
resulted in an action potential. The process of Na+ rushing into the cell may be thought
of as fueling the action, whereas the process of K + leaving the cell brakes the action
potential.
➢ In 1963, Hodgkin and Huxley received the Nobel Prize in Physiology or Medicine for this
research.
• We now know that changes in voltage regulate specific voltage-activated ion channels (also
called voltage-gated ion channels) in the plasma membrane of the axon and cell body.
➢ Biologists can study these channels by using the patch clamp technique to measure
currents across a very small segment of the plasma membrane rather than across the
entire membrane. The patch of membrane measured is so small that it may contain a
single channel.
• Biologists have used certain toxins that affect the nervous system to investigate how membrane
channels function.
➢ For example, the poison tetrodotoxin (TTX) binds to voltage-activated Na+ channels,
blocking the passage of Na+. Using TTX and other toxins, researchers were able to
identify the channel protein.
➢ TTX was first isolated from the Japanese puffer fish, which is eaten as a delicacy. In tiny
amounts TTX tingles the taste buds, but a slightly larger amount can prevent breathing.
(The Japanese government operates a certification program that teaches puffer fish
chefs to carefully remove the organs containing the toxin.)
• Investigators have established that voltage-activated ion channels have charged regions that act
as gates. Voltage-activated Na+ channels have two gates: an activation gate and an inactivation
gate. Voltage-activated K + channels have a single gate.
➢ Local anesthetics, such as procaine (novocaine) and lidocaine (Xylocaine) as well as
cocaine, bind to voltage-activated Na+ channels and block them.
➢ These blocked channels cannot open in response to depolarization, and the neuron
cannot transmit an impulse through the anesthetized region. Signals do not reach the
brain, so pain is not experienced.
An Action Potential is Generated When the Voltage Reaches
Threshold Level
• The membrane of most neurons can depolarize by about 15 mV—that is, to a potential of about
−55 mV—without initiating an action potential.
➢ However, when depolarization is greater than −55 mV, the threshold level is reached,
and an action potential is generated. The neuron membrane quickly reaches zero
potential and even overshoots to +35 mV or more as a momentary reversal in polarity
takes place.
➢ The sharp rise and fall of the action potential is called a spike.
• At resting potentials, activation gates of the voltage-activated Na+ channels are closed,
and Na+ cannot pass into the neuron.
• When the voltage reaches threshold level, the channel proteins change shape, opening the
activation gates. Sodium ions can then flow through the voltage-activated Na+ channels.
➢ As a result, the inside of the neuron becomes positively charged relative to the fluid
outside the plasma membrane, generating an action potential.
• Inactivation gates that are open in the resting neuron close slowly in response to depolarization.
Sodium ions can pass through the channel only during the brief period when both activation and
inactivation gates are open.
• The generation of an action potential depends on a positive feedback system. (In a positive
feedback system, a change in some condition triggers a response that intensifies the change.)
➢ When a neuron becomes depolarized, voltage-activated Na+ channels open, increasing
the membrane permeability to Na+. Sodium ions diffuse into the cell, moving from an
area of higher concentration to an area of lower concentration.
➢ As Na+ flow into the cell, the cytosol becomes positively charged relative to the
extracellular fluid. The positive charge further depolarizes the neuron so that more
voltage-activated Na+ channels open, which increases membrane permeability to Na+.
The Neuron Repolarizes and Returns to a Resting State
• After a certain period, inactivation gates close in the Na+ channels, and the membrane again
becomes impermeable to Na+. This inactivation begins the process of repolarization, during
which the membrane potential returns to its resting level.
➢ Voltage-activated K + channels slowly open in response to depolarization.
When Na+ have almost stopped rushing into the neuron, K + channels open,
and K + leak out of the neuron. This decrease in intracellular K + returns the interior of
the membrane to its relatively negative state, repolarizing the membrane. Voltage-
activated K + channels remain open until the resting potential has been restored.
• As a wave of depolarization moves down the membrane of the neuron, the normal polarized
state is quickly re-established behind it. The entire process—depolarization and then
repolarization—can take place in less than 1 millisecond.
• During the millisecond or so in which it is depolarized, the axon membrane is in
an absolute refractory period: it cannot transmit another action potential no matter how great
a stimulus is applied because the voltage-activated Na+ channels are inactivated. Until their
gates are reset, they cannot open again.
• When enough Na+ channel gates have been reset, the neuron enters a relative refractory
period that lasts for a few more milliseconds. During this period, the axon can transmit
impulses, but the threshold is higher (less negative). Even with the limits imposed by their
refractory periods, most neurons can transmit several hundred impulses per second.
• In summary, neural action proceeds as follows:

neuron in resting state ➝ stimulus causes depolarization ➝ threshold reached ➝ action potential
transmits signal ➝ repolarization and return to resting state

The Action Potential Is an All-Or-None Response

• Any stimulus too weak to depolarize the plasma membrane to threshold level cannot fire the
neuron. It merely sets up a local signal that fades and dies within a few millimeters from the
point of stimulus.
 • Only a stimulus strong enough to depolarize the membrane to its critical threshold level results
in transmission of an impulse along the axon.
➢ An action potential is an all-or-none response because either it occurs or it does not. No
variation exists in the strength of a single impulse.
• If the all-or-none law is valid, how can we explain differences in the levels of intensity of
sensations? After all, we have no difficulty distinguishing between the pain of a severe
toothache and that of a minor cut on the arm.
➢ We can explain this apparent inconsistency by understanding that the intensity of
sensation depends on several factors, including the number of neurons stimulated and
their frequency of discharge.
➢ For example, suppose that you burn your hand. If a large area is burned, more pain
receptors are stimulated and more neurons become depolarized. Also, each neuron
transmits more action potentials per unit of time.

An Action Potential Is Self-Propagating

• Once initiated, an action potential continues along the neuron. During depolarization, the
affected area of the membrane is more positive relative to adjacent regions where the
membrane is still at resting potential.
• The difference in potentials between active and resting membrane regions causes ions to flow
between them (an electric current). The flow of Na+ into the adjacent region induces the
opening of voltage-activated Na+ channels in that area of the membrane.
• The process is repeated like a chain reaction until the end of the axon is reached. Thus, an action
potential is a wave of depolarization that travels down the length of the axon.
➢ Transmission of an action potential is sometimes compared with a flame moving along a
trail of gunpowder. Once the gunpowder is ignited at one end of the trail, the flame
moves steadily to the other end by igniting the powder particles ahead of it. An amazing
difference is that after a brief refractory period, the neuron recovers and is able to
transmit another action potential.
Several Factors Determine the Velocity of an Action Potential
• Compared with the flow of electrons in electrical wiring or the speed of light, a nerve impulse
travels rather slowly.
➢ Most axons transmit impulses at about 1 to 10 m per second.
➢ The smooth, progressive impulse transmission just described, called continuous
conduction, occurs in unmyelinated neurons. In these axons, the speed of transmission
is proportional to the diameter of the axon.
• Axons with larger diameters transmit faster than those with smaller diameters because an axon
with a large diameter presents less internal resistance to the ions flowing along its length.
➢ Squids and certain other invertebrates have giant axons, up to 1 mm in diameter, which
allow them to respond rapidly when escaping from predators.
• In vertebrates, another strategy that speeds transmission has evolved—myelinated neurons.
Myelin acts as an effective electrical insulator around the axon. However, the axon is not
myelinated at the nodes of Ranvier.
➢ At these nodes, the plasma membrane of the axon makes direct contact with the
surrounding extracellular fluid. Voltage-activated Na+ and K + channels are
concentrated at the nodes. In fact, in myelinated neurons, ion movement across the
membrane occurs only at the nodes.
• The ion activity at an active node results in diffusion of ions along the axon that depolarize the
next node. The action potential appears to jump from one node of Ranvier to the next. This type
of impulse transmission is known as saltatory conduction (from the Latin word saltus, meaning
“to leap”).
• In myelinated neurons, the distance between successive nodes of Ranvier affects speed of
transmission. When nodes are farther apart, less of the axon must depolarize, and the axon
conducts the impulse faster.
➢ Using saltatory conduction, a myelinated axon can conduct an impulse up to 50 times
faster than the fastest unmyelinated axon.
➢ Saltatory conduction has another advantage over continuous conduction: it requires less
energy. Ions move across the plasma membrane only at the nodes, so
fewer Na+ and K + are displaced. As a result, the sodium–potassium pumps do not
expend as much ATP to re-establish resting conditions each time an impulse is
conducted.
41.4Transmitting Information across Synapses
• A synapse is a junction between two neurons or between a neuron and an effector (a muscle or
gland cell).
• A neuron that terminates at a specific synapse is called a presynaptic neuron, whereas a neuron
that begins at that synapse is a postsynaptic neuron.
➢ Note that these terms are relative to a specific synapse. A neuron that is postsynaptic
with respect to one synapse may be presynaptic to the next synapse in the sequence.

Signals Across Synapses Can Be Electrical or Chemical

• Based on how presynaptic and postsynaptic neurons communicate, two types of synapses have
been identified: electrical synapses and chemical synapses.
• In an electrical synapse, the presynaptic and postsynaptic neurons occur very close together
(within 2 nm of one another) and form gap junctions. The interiors of the two neurons are
physically connected by a protein channel.
➢ Electrical synapses let ions pass from one cell to another, permitting an impulse to be
directly and rapidly transmitted from a presynaptic to a postsynaptic neuron. The
escape responses of many animals involve electrical synapses.
➢ For example, the “tail-flick” escape response of the crayfish involves giant neurons in
the nerve cord that form electrical synapses with large motor neurons. The motor
neurons signal muscles in the abdomen to contract.
➢ Electrical synapses are important in the mammalian nervous system as well. For
example, many interneurons communicate by way of electrical synapses. They are also
found in cardiac muscle and in the retina.
• The majority of synapses are chemical synapses. Presynaptic and postsynaptic neurons are
separated by a space, the synaptic cleft, which is about 20 nm wide (less than one-millionth of
an inch).
➢ Depolarization is a property of the plasma membrane, so when an action potential
reaches the end of the axon, it cannot jump the gap. The electrical signal must be
converted into a chemical one.
➢ When an action potential reaches a synaptic terminal, it triggers the release of
a neurotransmitter, a chemical messenger that conducts the neural signal across the
synapse.
➢ Neurotransmitter molecules then bind to receptors that are chemically activated ion
channels in the membrane of the postsynaptic neuron. This binding triggers specific
gated ion channels to open (or close), resulting in changes in permeability of the
postsynaptic membrane.
➢ When a postsynaptic neuron reaches its threshold level of depolarization, it transmits an
action potential.

Neurons Use Neurotransmitters to Signal Other Cells

• Neurotransmitters signal other neurons, muscle fibers, or gland cells. About 100 different
neurotransmitters are known or suspected.
• We can categorize them in several chemical groups, including acetylcholine, biogenic amines,
amino acids, neuropeptides, and gaseous neurotransmitters.
• Acetylcholine is a low-molecular-weight neurotransmitter that is released from motor neurons
and triggers muscle contraction. Acetylcholine is also released by some neurons in the brain and
in the autonomic nervous system
➢ Cells that release acetylcholine are called cholinergic neurons.
 ➢ Neurons that release norepinephrine are called adrenergic
neurons. Norepinephrine, epinephrine, and the
neurotransmitter dopamine are catecholamines.
• The catecholamines and the neurotransmitters serotonin and histamine belong to a class of
compounds called biogenic amines.
➢ Biogenic amines affect mood, and their imbalance has been linked to several disorders,
including major depression, anxiety disorders, attention deficit hyperactivity disorder
(ADHD), and schizophrenia.
• Several amino acids function as neurotransmitters.
➢ Glutamate is the major excitatory neurotransmitter in the brain. One type of glutamate
receptor is the target of several mind-altering drugs, including phencyclidine (known as
PCP or “angel dust”).
➢ The amino acid glycine and a modified amino acid, gamma-aminobutyric acid (GABA),
are neurotransmitters that inhibit neurons in the spinal cord and brain.
o Glycine is the main inhibitory neurotransmitter in the spinal cord. GABA is the
neurotransmitter used at most rapid inhibitory synapses throughout the brain.
o Many drugs that reduce anxiety enhance the actions of GABA by permitting
lower concentrations of GABA to open Cl− channels. These drugs include
benzodiazepines, such as diazepam (Valium) and alprazolam (Xanax), and
barbiturates, such as phenobarbital.

• Neuropeptides, such as endorphins and enkephalins, appear to function mainly

as neuromodulators, messenger molecules that stimulate long-term changes that enhance or
inhibit synaptic function.
➢ Some neurobiologists consider them a group of neurotransmitters, but others classify
them as a separate group.
• Endorphins, such as beta-endorphin, and enkephalins are the body’s own endogenous opioids.
➢ Opiate drugs—for example, morphine and codeine—are powerful analgesics, drugs that
relieve pain without causing loss of consciousness.
➢ Endorphins and enkephalins bind to opioid receptors (the same receptors to which
opiate drugs bind) and block pain signals.
➢ Opioids modulate the effect of other neurotransmitters, including substance P, which
activates pathways that transmit pain signals from certain sensory neurons to the CNS.
• The signaling molecule nitric oxide (NO) is a gas that diffuses across cell membranes. It can
transmit information from the postsynaptic neuron to the presynaptic neuron, the opposite
direction of transmission from other neurotransmitters. Thus, it acts as a retrograde
messenger at some synapses.

Neurotransmitter Site of Action Action Comments

ACETYLCHOLINE CNS, Excitatory effect on skeletal Important role in learning and memory;
neuromuscular muscle; inhibitory effect on cardiacconcentration decreases in the brain
junctions muscle; excitatory or inhibitory at during the progression of Alzheimer’s
other sites disease; helps regulate both neural and
immune system function
BIOGENIC CNS, PNS Excitatory or inhibitory; Amphetamines stimulate release and
AMINES Norepinephrine concentration in brain affects block their reuptake; certain
mood, sleep, wakefulness, antidepressants also block reuptake;
attention; mainly inactivated by Ritalin (methylphenidate) stimulates
reuptake into axon terminal release
Dopamine CNS Helps maintain balance between Abnormal amounts in attention-deficit
excitation and inhibition of disorder and schizophrenia; amount
neurons; important in motor reduced in Parkinson’s disease;
function; concentration in brain amphetamines and cocaine stimulate
affects mood involved in motivation release and cocaine also inhibits
and reward reuptake
Serotonin (5- CNS Excitatory effect on pathways that Concentration highest during alert
hydroxytryptamine, 5-HT) control muscle action; inhibitory states; concentration lowest during
effect on sensory pathways; helps sleep; many antidepressants, for
regulate food intake, sleep, and example, Prozac (fluoxetine) and Zoloft
wakefulness; affects mood (paroxetine), block serotonin reuptake
Neurotransmitter Site of Action Action Comments
AMINO ACIDS Glutamate CNS, invertebrate Principal excitatory THC, the main psychoactive ingredient
neuromuscular neurotransmitter in vertebrate of cannabis, decreases glutamate
junctions brain; functions in learning and release
memory; excitatory effect at
invertebrate neuromuscular
junctions
Gamma-aminobutyric acid CNS, invertebrate Major inhibitory neurotransmitter Barbiturates and benzodiazepines
(GABA) neuromuscular in mammalian CNS increase effect of GABA
junctions
NEUROPEPTIDES Endorphins CNS, PNS Endogenous opiates; bind with Morphine-like
and enkephalins (opioids) opiate receptors; inhibit release of
substance P—this action inhibits
pain
Substance P CNS, PNS Activates pathways that transmit
pain signals
GASEOUS Most neurons? Diffuse across cell membranes;
NEUROTRANSMITTERS Nitric retrograde messengers; transmit
oxide, carbon monoxide, signals from postsynaptic to
hydrogen sulfide presynaptic neurons

Neurotransmitters Bind with Receptors on Postsynaptic Cells

• Neurotransmitters are stored in synaptic terminals within hundreds of small membrane-
enclosed sacs called synaptic vesicles.
➢ Each time an action potential reaches a synaptic terminal, voltage-gated Ca2+ channels
open. Calcium ions from the extracellular fluid then flow into the synaptic terminal.
The Ca2+ induce synaptic vesicles to fuse with the presynaptic membrane and release
neurotransmitter molecules into the synaptic cleft by exocytosis.
• Neurotransmitter molecules diffuse across the synaptic cleft and bind with specific receptors on
the dendrites or cell bodies of postsynaptic neurons (or on the plasma membranes of effector
cells). Many neurotransmitter receptors are chemically activated ion channels known as ligand-
gated channels.
➢ When the neurotransmitter, the ligand, binds with the receptor, the ion channel opens.
(Recall that a ligand is a molecule that binds to a specific site in a receptor.) The
acetylcholine receptor, for example, is a ligand-gated ion channel that permits the
passage of Na+ and K + .
• Some neurotransmitters, such as serotonin, operate by a different mechanism. They work
indirectly through a second messenger.
➢ Binding of the neurotransmitter with a receptor activates a G protein. The G protein
then activates an enzyme, such as adenylyl cyclase, in the postsynaptic membrane.
➢ Adenylyl cyclase converts ATP to cyclic AMP (cAMP), which acts as a second messenger.
Cyclic AMP activates a kinase that phosphorylates a protein, which then
closes K + channels.
• For a postsynaptic neuron to repolarize quickly, any excess neurotransmitter in the synaptic
cleft must be removed. Some neurotransmitters are inactivated by enzymes.
➢ For example, the enzyme acetylcholinesterase degrades excess acetylcholine into its
chemical components, choline and acetate.
➢ Other neurotransmitters, such as the biogenic amines, are actively transported back into
the synaptic terminals, a process known as reuptake. These neurotransmitters are
repackaged in vesicles and recycled.
• Many drugs inhibit the reuptake of neurotransmitters.
➢ For example, some antidepressant medications are selective serotonin reuptake
inhibitors (SSRIs). SSRIs such as fluoxetine (Prozac) and escitalopram (Lexapro)
selectively inhibit the reuptake of serotonin in the brain. This action concentrates
serotonin in the synaptic cleft, elevating mood.
➢ A few antidepressants inhibit the reuptake of both serotonin and norepinephrine or
serotonin and dopamine.
Activated Receptors Can Send Excitatory or Inhibitory Signals
• A postsynaptic neuron may have receptors for several types of neurotransmitters. Some of its
receptors may be excitatory, and others may be inhibitory.
➢ As a result, the same neurotransmitter can have different effects depending on the type
of postsynaptic receptor with which it combines.
➢ For example, acetylcholine has an excitatory effect on skeletal muscle and an inhibitory
effect on cardiac muscle.
• When neurotransmitter molecules bind to receptors, the activated receptor can directly or
indirectly open or close ion channels; this action changes the permeability of the postsynaptic
membrane to certain ions.
➢ The resulting redistribution of ions changes the electrical potential of the membrane,
and the membrane may depolarize.
➢ For example, when neurotransmitter molecules combine with receptors that
open Na+ channels, the resulting influx of Na+ partially depolarizes the membrane. If
sufficiently intense, a local depolarization can set off an action potential.
 • A change in membrane potential that brings the neuron closer to firing is called an excitatory
postsynaptic potential (EPSP).
➢ Imagine that sufficient sodium ions enter to change the membrane potential from −70
to −60 mV. The membrane would be only −5 mV away from threshold. Under such
conditions, an additional relatively weak stimulus, causing a small influx of Na+, can
cause the neuron to fire. Note that unlike action potentials, postsynaptic potentials are
graded responses.
• Some neurotransmitter–receptor combinations hyperpolarize the postsynaptic membrane,
causing the membrane potential to become more negative. Because such an action takes the
neuron farther away from the firing level, a potential change in this direction is called
an inhibitory postsynaptic potential (IPSP).
➢ For example, if the membrane potential changes from −70 to −80 mV, the membrane is
farther away from threshold, and a stronger stimulus is required to fire the neuron.
• Like an EPSP, an IPSP can be produced in several ways. Two types of GABA receptors are known
to produce IPSPs.
➢ When GABA binds to a GABA𝐵 receptor, K + channels open. As Na+ diffuse out, the
neuron becomes more negative, hyperpolarizing the membrane.
➢ Activated GABA𝐴 receptors produce IPSPs by opening Cl− channels. In this case, the
influx of negative ions hyperpolarizes the membrane. Although the mechanisms are
different, the inhibiting effect of GABA is the same in both cases.
• In summary, neural signaling across synapses involves the following sequence of events:

action potential reaches synaptic terminal ➝ calcium ions enter synaptic terminal ➝ synaptic vesicles
release neurotransmitter into the synaptic cleft ➝ neurotransmitter diffuses across synaptic cleft ➝
neurotransmitter binds with receptors in membrane of postsynaptic neuron ➝ ion channels open or
close, resulting in depolarization or hyperpolarization of postsynaptic membrane

41.5Neural Integration
• Each neuron may synapse with hundreds of other neurons. Indeed, thousands of synaptic
terminals of presynaptic neurons may cover as much as 40% of a postsynaptic neuron’s
dendritic surface and cell body.
➢ It is the job of the dendrites and the cell body of every neuron to integrate the messages
that continually bombard them.
• Neural integration is the process of summing, or integrating, incoming signals. EPSPs and IPSPs
are produced continually in postsynaptic neurons, and IPSPs cancel the effects of some EPSPs.
➢ It is important to remember that each EPSP and IPSP is not an all-or-none response.
Rather, each is a graded response that does not travel like an action potential but may
be added to or subtracted from other EPSPs and IPSPs.
• As the membrane of the postsynaptic neuron continuously updates its molecular tabulations,
the neuron may be inhibited or brought to threshold level. This mechanism integrates hundreds
of signals (EPSPs and IPSPs) before an action potential is actually transmitted along the axon of a
postsynaptic neuron.
➢ Local responses permit the neuron and the entire nervous system a far greater range of
response than would be possible if every EPSP generated an action potential.

Postsynaptic Potentials are Summed Over Time and Space

• Each EPSP or IPSP is a graded potential that varies in magnitude depending on the strength of
the stimulus applied. One EPSP is usually too weak to trigger an action potential by itself. Its
effect is below threshold level.
 ➢ However, even though subthreshold EPSPs do not produce an action potential, they do
affect the membrane potential. EPSPs can be added together in a process
called summation.
• Temporal summation occurs when a presynaptic neuron fires multiple times in rapid
succession, resulting in repeated stimulation of a postsynaptic neuron.
➢ New EPSPs develop before previous EPSPs have decayed. The summation of several
EPSPs may bring the neuron to the critical firing level.
• Spatial summation can also bring the postsynaptic neuron to threshold level. Spatial
summation is the summing of several postsynaptic potentials resulting when closely spaced
presynaptic neurons release neurotransmitter simultaneously.
➢ The postsynaptic neuron may be stimulated at multiple regions at the same time.
➢ Neurons sum IPSPs as well as EPSPs. As IPSPs occur, they move the membrane potential
farther away from threshold.

Where Does Neural Integration Take Place?

• On a molecular level, every neuron tabulates the thousands of bits of information that
continuously bombard it.
➢ In vertebrates more than 90% of the neurons in the body are located in the CNS, so
most neural integration takes place there, within the brain and spinal cord.
➢ These neurons are responsible for making most of the “decisions.”

41.6Neural Circuits: Complex Information

Signaling
• The CNS contains millions of neurons, but it is not just a tangled mass of nerve cells. Its neurons
are functionally arranged in specific pathways, or neural circuits.
➢ A neural circuit typically consists of one or more afferent neurons, one or more
interneurons, and one or more efferent neurons.
• Neural circuits are organized into neural networks. Although each network has some specific
characteristics, the neural circuits in all the networks share many organizational features.
➢ For example, convergence and divergence are characteristic of them all.
• In convergence of neural input, a single neuron receives converging signals (inputs) from two or
more presynaptic neurons.
➢ An interneuron in the spinal cord, for instance, may receive converging information
from sensory neurons entering the spinal cord, from neurons bringing information from
various parts of the brain, and from neurons coming from different levels of the spinal
cord.
➢ Information from all these sources must be integrated before an action potential is
transmitted and an appropriate motor neuron is stimulated.
• In divergence of neural input, a single presynaptic neuron makes connections with many
postsynaptic neurons. Each presynaptic neuron may branch and synapse with thousands of
different postsynaptic neurons.
➢ For example, a single neuron transmitting an impulse from the motor area of the brain
may make connections with hundreds of interneurons in the spinal cord, and each of
them may diverge, in turn, so that hundreds of muscle fibers are stimulated.