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Epilepsy
Focus on Disorders
Three symptoms are found in many kinds of epilepsy:
1. The victim often experiences an aura, or warning, of an
impending seizure, which may take the form of a sensation,
such as odors or sounds, or may simply be a
“feeling.”
2. The victim may lose consciousness and later be unaware
that the seizure ever happened.
3. The seizure is often accompanied by abnormal movements
such as repeated chewing or shaking, twitches
that start in a limb and spread across the body, and, in
some cases, a total loss of muscle tone and postural
support, causing the person to collapse.
J.D.
worked as a disc jockey for a radio station and
did so for parties in his off-hours. One evening
he set up on the back of a truck at a rugby field to emcee a
jovial and raucous rugby party. Between musical sets, he
made introductions, told jokes, and exchanged toasts and
jugs of beer with the partyers.
About one o’clock in the morning, J. D. suddenly collapsed,
making unusual jerky motions, and then passed
out. He was rushed to a hospital emergency room, where
he gradually recovered. The attending physician noted that
he was not drunk, released him to his friends, and recommended
a series of neurological tests for the next day. Subsequent
state-of-the-art brain scans indicated no obvious
brain injury or tumor.
The key to diagnosing J. D.’s problem lay in an older
technology based on the small electrical signals given off
by the brain. Sensitive recording machines, such as the electroencephalograph
developed in the 1930s, can detect
those signals. When the electrical activity in J. D.’s brain was
recorded while a strobe light was flashed before his eyes,
the electroencephalogram displayed a series of abnormal
electrical patterns characteristic of epilepsy, graphed in the
accompanying illustration.
The doctor prescribed Dilantin (diphenylhydantoin),
an anesthetic agent given in low doses, and advised J. D. to
refrain from drinking. He was required to give up his driver’s
license to prevent the possibility that an attack while
driving could cause an accident. And he lost his job at the
radio station. After 3 months of uneventful drug treatment,
he was taken off medication and his driver’s license was restored.
Eventually J. D. convinced the radio station that he
could resume work, and, in the past 10 years, he has been
seizure-free.
One person in 20 will experience an epileptic seizure
in his or her lifetime. Synchronous stimuli can trigger a
seizure; thus a strobe light is often used in diagnosis. Some
epileptic seizures are symptomatic—they can be linked to
a specific cause, such as infection, trauma, tumor, or other
damage to a part of the brain. Idiopathic seizures (related
to the individual person) appear to arise spontaneously.
Their cause is poorly understood.
EEG patterns recorded during the stages of a grand mal
seizure: (1) normal pattern before the seizure; (2) onset of
seizure; (3) clonic phase in which the person makes rhythmic
movements in time with the large, abnormal electrical
discharges; (4) period of coma after the seizure ends. Color
dots on the approximate recording sites of the cortex are
coded to the recordings. Abbreviations: LT and RT, left and right
temporal; LF and RF, left and right frontal; LO and RO, left and
right occipital. Adapted from Fundamentals of Human Neuropsychology
(p. 80), by B. Kolb and I. Q. Whishaw, 1980, San Francisco: W. H. Freeman and
Company.
Left Right
LT
LT RT
LF RF
LO RO
1 2 3 4
RT
LF
RF
LO
RO
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If seizures occur repeatedly and cannot be controlled
by drug treatment, surgery may be performed. The goal of
surgery is to remove damaged or scarred tissue that serves
as the focal point of a seizure. Removing this small area
prevents seizures from starting and spreading to other brain
regions.
Seizures may be categorized according to the severity
of these symptoms. In petit mal (from the French for “little
bad”) seizures, there is usually a brief loss of awareness and
small or brief abnormal movements. In contrast, grand mal
(“big bad”) seizures entail severe abnormalities of movement,
collapse, and loss of consciousness.
Figure 4-1, perhaps the most reproduced drawing in behavioral neuroscience, is
nearly 350 years old. Taken from René Descartes’s book titled Treatise on Man,
it illustrates the first serious attempt to explain how information travels through
the nervous system.Descartes proposed that the carrier of information is cerebrospinal
fluid flowing through nerve tubes.
When the fire burns the man’s toe, Descartes reasoned, it stretches the skin, which
tugs on a nerve tube leading to the brain. In response to the tug, a valve in a ventricle
of the brain opens and CSF flows down the tube, filling the leg muscles and causing
them to contract and pull the toe back from the fire. The flow of fluid through other
tubes to other muscles of the body (not shown in Figure 4-1) causes the head to turn
toward the painful stimulus and the hands to rub the injured toe.
As you learned in Chapter 1,Descartes’s theory was inaccurate, yet it is remarkable
because he isolated the three basic questions that underlie a behavioral response:
1. How do our nerves detect a sensory stimulus and inform the brain about it?
2. How does the brain decide what response should be made?
3. How does the brain command muscles to move to produce a behavioral response?
Descartes was trying to explain the very same things that we want to explain today.
If it is not stretched skin tugging on a nerve tube that initiates the message, the message
must still be initiated somehow. If it is not the opening of valves to initiate the flow
of CSF to convey information, the information must still be sent. If it is not the filling
of muscles with fluid that produces movements, some other mechanism must still
cause muscles to contract.
What all these mechanisms in fact are is the subject of this chapter. We examine
how neurons convey information from the environment throughout the nervous system
and ultimately activate muscles to produce movement. Then we describe how researchers
use electrical activity to study brain function. We begin by explaining the
electrical activity of the nervous system.
ELECTRICITY AND NEURONS
The first hints about how the nervous system conveys its messages came in the eighteenth
century after the discovery of electricity. You have extensive experience with
electricity, which powers the lights in your home and the batteries that run so many
Figure 4-1
Descartes’s Theory of Information
Flow From Descartes, 1664.
112 ! CHAPTER 4
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gadgets. In technical terms, electricity is a flow of electrons from a body that contains
a higher charge (more electrons) to a body that contains a lower charge (fewer electrons),
and this electron flow can perform work.
The body with the higher electrical charge is the negative pole, because electrons
are negatively charged and this body has more of them. The body with the lower electrical
charge is the positive pole. Electrical potential, measured in volts, describes the
difference in charge between the two poles. (The term potential is used because the
electrons on the negative pole have the potential to flow to the positive pole. The negatively
charged electrons are attracted to the positive pole because opposite charges
attract.)
Each wall socket in your house has a positive and a negative pole. Similarly, if you
look at a battery, you will see that one of its poles is marked “!” for negative and the
other “"” for positive. The poles are separated by an insulator, a substance through
which electrons cannot flow. Therefore, a flow, or current, of electrons streams from the
negative (!) to the positive (") pole only if the two poles are connected by a conducting
medium, such as a bare wire. If a wire, or electrode, from each pole is brought
into contact with biological tissue, current will flow from the wire connected to the negative
pole into the tissue and then from the tissue into the wire connected to the positive
pole.
Electrons can accumulate on many substances, including our bodies, which is why
you sometimes get a shock from touching a metal object after walking on a carpet.
From the carpet, you accumulate relatively loose electrons, which give your body a
greater negative charge than that of objects around you. In short, you become a negative
pole.
Electrons normally leave your body as you walk around, because the earth acts as
a positive pole. If you are wearing rubber-soled shoes, however, you retain electrical potential
because the rubber acts as an insulator. If you then touch a metal object, such
as a water fountain, electrons that are equally distributed on your body suddenly rush
through the contact area of your fingertips. In fact, if you watch your fingertips just before
they touch the water fountain, you will see a small spark as the electrons are transferred.
These electrons leaving your fingertips give you the shock.
Combing your hair is another way to accumulate electrons. If you then hold a piece
of paper near the comb, the paper will bend in the comb’s direction. The negative
charges on the comb have pushed the paper’s negative charges to the back side of the
paper, leaving the front side positively charged. Because unlike charges attract, the
paper bends toward the comb.
Discoveries on the nature of electricity quickly led to proposals that electricity
plays a role in conducting information in the nervous system. In the next section, we
describe a few milestones that lead from this idea to an understanding of how the nervous
system really conveys information.
Early Clues to Electrical Activity in
the Nervous System
In 1731, Stephen Gray performed an experiment similar to the comb experiment just
described. He rubbed a rod with a piece of cloth to accumulate electrons on the rod.
Then he touched the charged rod to the feet of a boy suspended on a rope and brought
a metal foil to the boy’s nose. The foil bent on approaching the boy’s nose, being attracted
to it, and, as foil and nose touched, electricity passed from the rod, through the
boy, to the foil.
HOW DO NEURONS TRANSMIT INFORMATION? ! 113
Electricity. The flow of electrons.
Negative pole. The source of electrons.
Positive pole. Location to which
electrons flow.
Electrical potential. An electrical
charge; the ability to do work through the
use of stored potential electrical energy.
Volt. A measure of a difference in
electrical potential.
Current. The flow of electrons from a
region of high negative charge to a region
of low negative charge; the flow of
various ions across the neuron
membrane.
Electrode. An iInsulated wire or a
saltwater-filled glass tube that is used to
stimulate or record from neurons.
Visit the Brain and Behavior Web site
(www.worthpublishers.com/kolb)
and go to the Chapter 4 Web links for an
introductory review of bioelectricity.
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Yet the boy was completely unaware that the electricity had passed through his
body. Therefore, Gray speculated that electricity might be the messenger in the nervous
system. Although this conclusion was not precisely correct, two other lines of evidence
implicated electrical activity in the nervous system’s flow of information. One of these
lines of evidence consisted of the results of electrical-stimulation studies, the other of
the results of electrical-recording studies.
ELECTRICAL-STIMULATION STUDIES
When eighteenth-century Italian scientist Luigi Galvani observed that frogs’ legs hanging
on a wire in a market twitched during a lightning storm, he surmised that sparks
of electricity from the storm were activating the muscles. Investigating this possibility,
he found that, if an electrical current is applied to a dissected nerve, the muscle to
which the nerve is connected contracts. Galvani concluded that the electricity flows
along the nerve to the muscle. This observation provoked a huge debate among scientists
concerning what he had actually found, and this debate pointed them in the direction
of understanding how nerves conduct information.
Many other researchers used Galvani’s technique of electrical stimulation to produce
muscle contraction. The technique requires a battery or other source of electrons
that delivers an electrical current. Figure 4-2A illustrates such an electrical stimulator
that transforms the 120-volt current from a wall socket into a current ranging from 2
to 10 volts, which will not damage cells.
Timers allow the stimulator to deliver either a single pulse of current lasting about
1/100 of a second or a series of these brief pulses. Wire leads connected to the stimulator’s
negative and positive poles carry the electrical current. One lead is attached to a
stimulating electrode, which is usually a wire (or a specially constructed glass tube) insulated
except for the tip that comes in contact with the cells to be stimulated. The
other lead (called the reference), attached to the positive pole, is placed on some other
part of the body.When the stimulator is on, the flow of electricity out of the tip of the
electrode onto the cells is enough to produce a physiological response.
In the mid-nineteenth century, two Prussian scientists, Gustave Theodor Fritsch
and Eduard Hitzig, demonstrated that electrical stimulation of the neocortex causes
movement. They studied several animal species, including rabbits and dogs, and may
even have stimulated the neocortex of a person, whom they were treating for head injuries
on a Prussian battlefield. They observed movements of the arms and legs of their
subjects in response to the stimulation of the neocortex.
In 1874, Robert Bartholow, a Cincinnati physician, wrote the first report describing
the effects of human brain stimulation.His patient,Mary Rafferty, had a skull defect
114 ! CHAPTER 4
(A) The flow of electricity
through the stimulating
electrode provides sufficient
current to produce a
physiological response.
Stimulator
Stimulating
electrode
Current
flow
Uninsulated
tip
Reference Reference
Nerve
A difference in voltage between the tip
of the recording electrode and a
reference electrode, deflects a needle
that indicates the voltage of the
current.
(B)
Voltmeter
Recording
electrode
Current
flow
Figure 4-2
Electrical Activity in Animal Tissue
(A) In electrical stimulation, current
(electrons) leaves the stimulator through
a wire lead (red) that attaches to an
electrode. From the uninsulated tip of
the electrode, the current enters the
tissue and, in doing so, stimulates it. A
second lead (green) is connected to a
reference electrode into which the
current flows back to the stimulator. The
reference electrode contacts a relatively
large surface area that spreads out the
current and therefore does not excite
the tissue here. (B) In electrical
recording, a voltmeter measures
electrical current.
Electrical stimulation. Passing an
electrical current from the tip of an
electrode through brain tissue, resulting in
changes in the electrical activity of the
tissue.
Visit the Foundations of Behavioral
Neuroscience CD and find the area on
electrical brain stimulation in the module
on research methods. You’ll see a model
of an electrical stimulator and a video
clip of the self-stimulation of a rat. (See
the Preface for more information about
this CD.)
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that exposed part of her neocortex. Bartholow stimulated her exposed brain tissue to
examine the effects. In one of his observations he wrote:
Passed an insulated needle into the left posterior lobe so that the non-insulated
portion rested entirely in the substance of the brain. The reference was
placed in contact with the dura mater.When the circuit was closed, muscular
contraction in the right upper and lower extremities ensued. Faint but visible
contraction of the left eyelid, and dilation of the pupils, also ensued. Mary
complained of a very strong and unpleasant feeling of tingling in both right
extremities, especially in the right arm, which she seized with the opposite
hand and rubbed vigorously. Notwithstanding the very evident pain from
which she suffered, she smiled as if much amused. (Bartholow, 1874)
Bartholow’s report was not well received. An uproar after its publication forced
him to leave Cincinnati. Nevertheless, he had demonstrated that the brain of a conscious
person could be stimulated electrically to produce movement of the body.
In the twentieth century, brain stimulation became a standard part
of many neurosurgical procedures. In particular, after the method had
been perfected in experimental animal studies,Wilder Penfield, a neurosurgeon
at the Montreal Neurological Institute, used electrical stimulation
to map the neocortex of surgery patients in the 1950s. The maps
that he produced allowed him to determine the function of various neocortical
regions and so to minimize the removal of undamaged tissue.
Penfield especially wanted to locate language areas in the neocortex to
be able to spare them during surgery.
ELECTRICAL-RECORDING STUDIES
Another line of evidence that the flow of information in the brain is partly electrical in
nature came from the results of recording experiments with the use of a voltmeter, a device
that measures the flow and the strength of electrical voltage.As illustrated in Figure
4-2B, the voltmeter has one wire connected to a recording electrode and a second connected
to a reference electrode,much as an electrical stimulator does. Any difference in
voltage between the tip of the recording electrode and the reference causes a current to
flow through the voltmeter, deflecting a needle that indicates the voltage of the current.
Richard Caton, a Scottish physician who lived in the late nineteenth and early
twentieth centuries, was the first to attempt to measure the electrical currents of the
brain with a sensitive voltmeter. He reported that, when he placed electrodes on the
skull of a human subject, he could detect fluctuations in his voltmeter recordings.
Today this type of brain recording, the electroencephalogram (EEG), is a graph of the
brain’s electrical activity, and the electroencephalograph is a standard tool for measuring
brain activity.
The results of electrical-recording studies provided evidence that
neurons send electrical messages, but concluding that nerve tracts
carry conventional electrical currents through the body proved problematic.
Hermann von Helmholtz, a nineteenth-century German scientist,
developed a procedure for measuring the speed of information
flow in a nerve. He stimulated a nerve leading to a muscle and measured
the time that it took the muscle to contract. The time was extremely
long. The nerve conducted information at the rate of only 30
to 40 meters per second, whereas electricity flows along a wire at the
much faster speed of light (3 # 108 meters per second).
The flow of information in the nervous system, then, is much too slow to be a flow
of electricity.And there is another problem.When current is passed between electrodes
HOW DO NEURONS TRANSMIT INFORMATION? ! 115
Wilder Penfield
(1891–1976)
Voltmeter. A device that measures the
difference in electrical potential between
two bodies.
Electroencephalogram (EEG).
Electrical brain graph that records
electrical activity through the skull or
from the brain and represents graded
potentials of many neurons.
Hermann von Helmholtz
(1821–1894)
On the Foundations CD, find the EEG
section in the module on research
methods. Investigate a model of an
electroencephalograph and view EEG
recordings.
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116 ! CHAPTER 4
placed on the brain to produce movement in a limb, the electrical current flows directly
between those electrodes. So how do muscles that are a considerable distance away
from the electrodes come to move?
To explain the electrical signals of a neuron, Julius Bernstein suggested in 1886 that
neurons have an electrical charge that can change and move and that the electrical
charge has a chemical basis. This suggestion led to the idea that modifications of a neuron’s
charge travel along the axon as a wave. Successive waves constitute the message that
the neuron conveys.
Notice that it is not the charge but the wave that travels along the axon. To understand
the difference, consider other kinds of waves. If you drop a stone into a pool of
water, the contact made by the stone hitting the water produces a wave that travels away
from the site of impact, as shown in Figure 4-3. The water itself does not travel. Only
the change in pressure moves, changing the height of the surface of the water and creating
the wave effect.
Similarly, when you speak, you induce pressure waves in air, and these waves carry
the “sound” of your voice to a listener. If you flick a towel, a wave travels to the other
end of the towel. Just as waves through the air send a spoken message, waves of chemical
change travel along an axon to deliver a neuron’s message.
Modern Tools for Measuring a Neuron’s
Electrical Activity
We do not feel waves of neural activity traveling around our bodies because the waves
that carry nervous system messages are very small and are restricted to the surfaces of
neurons. Still, we can measure such waves and determine how they are produced, by
using electrical-stimulation and -recording techniques. If an electrode connected to a
voltmeter is placed on a single axon, the electrode can detect a change in electrical
charge on that axon’s membrane as the wave passes, as illustrated in Figure 4-4.
As simple as this process may seem, it was successfully carried out only after a few
other discoveries had been made. The procedure requires a neuron large enough to
record, a recording device sufficiently sensitive to detect a very small electrical impulse,
and an electrode small enough to place on the surface of a single neuron. The discovery
of the giant axon of the squid, the invention of the oscilloscope, and the development
of microelectrodes met all these requirements.
THE GIANT AXON OF THE SQUID
The neurons of most animals, including humans, are tiny, on the order of 1 to 20 micrometers
(1–20 lm) in diameter, too small to be seen by the eye and too small to perform
experiments on easily. British zoologist J. Z. Young, when dissecting the North
Atlantic squid, Loligo, noticed that it has truly giant axons, as much as a millimeter
(1000 lm) in diameter. Figure 4-5 illustrates Loligo and the giant axons leading to its
body wall, or mantle, which contracts to propel the squid through the water.
Electrical
charge
Incoming
signal
Voltmeter
Outgoing
signal
–
–
–
–
– –
– –
– –
– –
– –
–
–
–
–
–
–
Figure 4-4
Wave of Information Neurons can
convey information as a wave induced
by stimulation on the cell body
traveling down the axon to its terminal.
A voltmeter detects the passage of
the wave.
Figure 4-3
Wave Effect Waves created
by dropping a stone in water
do not entail the forward
movement of the water but
rather differences in pressure
that change the height of the
surface of the water.
Young-Wolff/PhotoEdit
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Loligo is not a giant squid. It is only about a foot long. But its axons are giants as
axons go. Each axon is formed by the fusion of many smaller axons. Because larger axons
send messages faster than smaller axons do, these giant axons
allow the squid to jet propel away from predators.
In 1936, Young suggested to Alan Hodgkin and Andrew
Huxley, two neuroscientists at Cambridge University in England,
that Loligo’s axons were large enough to use for electrical-
recording studies. A giant axon could be dissected out of
the squid and kept functional in a bath of salty liquid that
approximates body fluids. In this way, Hodgkin and Huxley
easily studied the neuron’s electrical activity.
THE OSCILLOSCOPE
Hodgkin and Huxley’s experiments were made possible by the invention of the oscilloscope.
You are familiar with one form of oscilloscope, a conventional television set. An
oscilloscope can also be used as a sensitive voltmeter to measure the very small and
rapid changes in electrical currents that come from an axon.
The important component of an oscilloscope is its glass vacuum tube. In the tube,
from which air is removed, a beam of negatively charged electrons is projected onto the
tube’s phosphorus-painted screen. When the electrons hit the paint, the phosphorus
glows momentarily.Moving the beam of electrons around leaves a visible trace on the
screen that lasts a second or so.
The trace is produced by changing the charge on two pairs of metal plates. The
members of each pair are positioned opposite one another on the inner surface of the
tube, as shown in Figure 4-6A. Changing the charges on the vertical pair of plates, located
on the tube’s sides, pushes the electron beam away from the negative pole toward
the positive pole,which leaves a horizontal line on the screen.
Oscilloscope. A device that measures
the flow of electrons to measure voltage.
Alan Hodgkin
(1914–1988)
Andrew Huxley
(b. 1917)
(A) (B)
Stellate
ganglion
Water forced
Mantle out for propulsion
Giant axon axons
Figure 4-5
Laboratory Specimen (A) The North
Atlantic squid propels itself both with
fins and by contracting its mantle to
force water out for propulsion. (B) The
stellate ganglion projects giant axons to
contract the squid’s mantle.
On the Foundations CD, find the
section on the membrane potential in the
module on neural communication. In the
animations showing resting potential and
action potential, you will view output
from an oscilloscope used for neural
recording. Note that the oscilloscope
changes in electrical potential when the
cell is stimulated.
Squid axon
Sweep
generator
Electron
gun Beam of
electrons
Vertical
plates
Horizontal
plates
Vacuum
tube
Reference
electrode
Recording
electrode Screen
30
Time (ms)
Voltage (mV)
(A) (B)
–70
0
S
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
+
–
Figure 4-6
Oscilloscope Recording (A) Changes in electrical current across the cell membrane
deflect the electron beam in the oscilloscope’s vertical plane. (B) The graph of a trace,
where S stands for stimulation. The horizontal axis measures time, and the vertical axis
measures voltage. The voltage of the axon shown in part A is represented as !70 mV.
William Jorgensen/Visuals Unlimited
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One metal plate of the horizontal pair is located at the top of the tube; the other is located
at the bottom.One horizontal plate is connected to the recording electrode and the
other to a reference electrode. Any electrical change between these two electrodes drives
the beam of electrons up and down, leaving a vertical line on the screen.
To visualize how recordings are made with an oscilloscope, imagine aiming a hose at
a brick wall. The spray of water is analogous to the beam of electrons.Moving the hose
horizontally leaves a horizontal spray on the wall, whereas moving the hose vertically
leaves a vertical spray.The water line on the wall is analogous to the phosphorus line traced
by the oscilloscope’s electron beam.
If you move the hose horizontally at a constant rate across the wall and then block
the water temporarily and start again, each horizontal sweep provides a measure of
time. Now imagine that someone bumps your arm upward as you make a horizontal
sweep, deflecting the trace as it sweeps across the wall. The time during which the trace
is deflected away from the horizontal baseline indicates how long the bump lasted, and
the height of the deflection indicates the size of the bump.
An oscilloscope operates in a very similar way. The charge on the vertical poles is
controlled by a timer, whereas the horizontal poles are connected to the preparation
from which the recording is being made. A vertical deflection of the trace, either up or
down, indicates a change in electrical activity on the preparation.Measuring the duration
of this deflection tells how long the electrical change lasts, whereas measuring the
size of the deflection tells you the magnitude of the change.
The advantage of using an oscilloscope instead of a voltmeter with a mechanical
needle is that an oscilloscope can record extremely small and rapid events, such as those
that take place in an axon. The scales used when recording from an axon, graphed in
Figure 4-6B, are milliseconds (1 ms $ one-one thousandth of a second) and millivolts
(1 mV $ one-one thousandth of a volt). Today, computers that measure small electrical
currents have replaced the oscilloscope.
MICROELECTRODES
The final ingredient needed to measure a neuron’s electrical activity is a set of electrodes
small enough to place on or into an axon. Such microelectrodes can also be used
to deliver an electrical current to a single neuron. One way to make a microelectrode
is to etch the tip of a piece of thin wire to a fine point and insulate the rest of the wire.
The tip is placed on or into the neuron, as illustrated at the top of Figure 4-7.
Microelectrodes can also be made from a thin glass tube. If the middle of the tube
is heated while the ends of the tube are pulled, the middle stretches as it turns molten,
and eventually breaks, producing two pieces of glass tubing, each tapered to a very fine
tip. The tip of a glass microelectrode can be as small as 1 lm, even though it still remains
hollow. When the glass tube is then filled with salty water, which provides the
conducting medium through which an electrical current can travel, it acts as an electrode.
Figure 4-7 (top) also shows a glass microelectrode containing a salt solution. A
wire placed in the salt solution connects the electrode to an oscilloscope.
Microelectrodes are used to record from an axon in a number of different ways.
Placing the tip of a microelectrode on an axon provides an extracellular measure of the
electrical current from a very small part of the axon. If a second microelectrode is used
as the reference, one tip can be placed on the surface of the axon and the other inserted
into the axon. This technique provides a measure of voltage across the cell membrane.
A still more refined use of a glass microelectrode is to place its tip on the neuron’s
membrane and apply a little back suction until the tip becomes sealed to a patch of the
membrane, as shown in the bottom panels of Figure 4-7. This technique is analogous
to placing a soda straw against a piece of plastic wrapping and sucking back to grasp
the plastic. This method allows a recording to be made only from the small patch of
membrane that is sealed within the perimeter of the microelectrode tip.
118 ! CHAPTER 4
To see a model and a video clip
demonstrating how microelectrodes are
used, visit the section on microelectrodes
in the research methods module on the
Foundations CD.
Microelectrode
Ion
channel
Membrane
To stimulation
or recording
device
Conducting
fluid such
as salt
water
Open tip
Insulation
Uninsulated
wire tip
Wire
Glass
Squid axon
Figure 4-7
Uses of Microelectrodes (Top, not
to scale) A squid axon is larger than the
tip of either a wire (left) or a glass
(right) microelectrode. Both types of
electrodes can be placed on an axon or
into it. (Bottom) One way to use a
microelectrode is to record from only a
small piece of an axon by pulling the
membrane up into the glass electrode
through suction.
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Using the giant axon of the squid, an oscilloscope, and microelectrodes,Hodgkin and
Huxley recorded the electrical voltage on an axon’s membrane and explained the nerve
impulse. The basis of this electrical activity is the movement of intracellular and extracellular
ions,which carry positive and negative charges. So to understand Hodgkin and Huxley’s
results, you first need to understand the principles underlying the movement of ions.
How the Movement of Ions Creates
Electrical Charges
As you learned in Chapter 3, the intracellular and extracellular fluid of a neuron is filled
with various charged ions, including positively charged Na" (sodium) and K" (potassium),
and negatively charged Cl! (chloride) ions. These fluids also contain numerous
negatively charged protein molecules (A! for short). Positively charged ions are called
cations, and negatively charged ions are called anions. Three factors influence the
movement of anions and cations into and out of cells: diffusion, concentration gradient,
and charge.
Because molecules move constantly, they spontaneously tend to spread out from
where they are more concentrated to where they are less concentrated. This spreading
out is diffusion. Requiring no work, diffusion results from the random motion of molecules
as they move and bounce off one another to gradually disperse in a solution.
When diffusion is complete, a dynamic equilibrium, with an equal number of molecules
everywhere, is created.
Smoke from a fire gradually diffuses into the air of a room, until every bit of air contains
the same number of smoke molecules. Dye poured into water diffuses in the same
way—from its point of contact to every part of the water in the container. Recall from
Chapter 3 that salts placed in water dissolve into ions surrounded by water molecules.Carried
by the random motion of the water molecules, the ions diffuse throughout the solution
to equilibrium,when every part of the container has exactly the same concentration.
Concentration gradient describes the relative concentration of a substance in
space. As illustrated in Figure 4-8A, drop a little ink into a beaker of water, and the dye
starts out concentrated at the site of contact and then spreads. The ink diffuses from a
point of high concentration to points of low concentration until it is equally distributed,
and all the water in the beaker is the same color.
A similar process takes place when a salt solution is placed into water. The salt concentration
is initially high in the location where it enters the water, but it then diffuses
from that location until its ions are in equilibrium. You are familiar with other kinds
of gradients. For example, a car parked on a hill will roll down the grade if it is taken
out of gear.
Because ions carry an electrical charge and similar charges repel each other, ion
movement can be described either by a concentration gradient or a voltage gradient,
the difference in charge between two regions that allows a flow of current if the two
regions are connected. Ions will move down a voltage gradient from an area of high
charge to an area of lower charge, just as they move down a
concentration gradient from an area of high concentration to
an area of lower concentration. Figure 4-8B illustrates this
process: when salt is dissolved in water, its diffusion can be
described as either movement down a concentration gradient
(for sodium and chloride ions) or movement down a
voltage gradient (for the positive and negative charges). In a
container such as a beaker, which allows unimpeded movement
of ions, the positive and negative charges eventually
balance.
HOW DO NEURONS TRANSMIT INFORMATION? ! 119
Visit the module on neural
communication on the Foundations CD.
In the section on the membrane potential
you’ll see an animation of action potential
showing how electrical and concentration
gradients mediate ionic movement
through a membrane. Note the changes
on the oscilloscope as ions flow into and
out of the cell.
Diffusion. Movement of ions from an
area of high concentration to an area
of low concentration through random
motion.
Concentration gradient. Differences
in concentration of a substance among
regions of a container that allows the
substance to diffuse from an area of
high concentration to an area of low
concentration.
Voltage gradient. Difference in charge
between two regions that allows a flow of
current if the two regions are connected.
(B)
Salt water
+ – + – + – +
– + – + – + – +
–
–
–
–
–
–
–
– –
–
–
–
–
–
+
+
+
+
+
+
+ +
+
+
+
+ +
+
+ – + – + – +
+ – + – + – + – +
+ – + – + – +
+ – + – + – + – +
+ – + – + – +
–
–
(A)
Ink
Time Time
Figure 4-8
Moving to Equilibrium (A) A
concentration gradient. When you
drop a small amount of ink into a
beaker of water, the ink will flow away
from the point of contact, where it has
a high concentration, into areas of
low concentration until it is equally
distributed in the beaker. (B) An
electrostatic gradient. Pouring a salty
solution into water frees its positive
and negative ions to flow down their
electrostatic gradients until positive and
negative charges are everywhere equal.
CH04.qxd 1/28/05 10:02 AM Page 119
A lack of impediment is not the case in intracellular
and extracellular fluid, because the
semipermeable cell membrane acts as a partial
barrier to the movement of ions between a cell’s
interior and exterior. As described in Chapter 3,
a cell membrane is composed of a phospholipid
bilayer, with the hydrophobic tails of one layer
pointing inward toward those of the other layer
and the hydrophilic heads pointing outward. This membrane is impermeable to salty
solutions because the salt ions, which are surrounded by water molecules, will not pass
through the membrane’s hydrophobic tails.
An imaginary experiment illustrates how a cell membrane influences the movement
of ions in this way. Figure 4-9A shows a container of water divided in half by a
solid membrane. If we place a few grains of salt (NaCl) in the left half of the container,
the salt dissolves and the ions diffuse down their concentration and voltage gradients
until the water is in equilibrium. In the left side of the container, there is no
longer a gradient for either sodium or chloride ions, because the water everywhere is
equally salty. There are no gradients for these ions on the other side of the container
either, because the membrane prevents the ions from entering that side. But there are
concentration and voltage gradients for both sodium and chloride ions across the
membrane—that is, from the salty side to the fresh-water side.
Recall that protein molecules embedded in a cell membrane form channels that act
as pores to allow certain kinds of ions to pass through the membrane. Returning to our
imaginary experiment, we place a couple chloride channels in the membrane that divides
the container of water, as illustrated at the left in Figure 4-9B. Chloride ions will
now cross the membrane and move down their concentration gradient on the side of
the container that previously had no chloride ions, shown in the middle of Figure 4-9B.
The sodium ions, in contrast, will not be able to cross the membrane. (Although
sodium ions are smaller than chloride ions, sodium ions have a greater tendency to
stick to water molecules and so they are bulkier and will not pass through a small chloride
channel.)
If the only factor affecting the movement of chloride ions were the chloride concentration
gradient, the efflux (outward flow) of chloride from the salty to the unsalty
side of the container would continue until chloride ions were in equilibrium on
both sides. But this is not what actually happens. Because the chloride ions carry a
negative charge, they are attracted back toward the positively charged sodium ions
(opposite charges attract). Consequently, the concentration of chloride ions remains
higher in the left side of the container than in the right, as illustrated on the right
Figure 4-9B.
The efflux of chloride ions down the chloride concentration gradient is counteracted
by the influx (inward flow) of chloride ions down the chloride voltage gradient.
At some point, equilibrium is reached in which the concentration gradient of chloride
ions is balanced by the voltage gradient of chloride ions. In brief:
concentration gradient $ voltage gradient
At this equilibrium, there is a differential concentration of the chloride ions on the two
sides of the membrane, the difference in ion concentration produces a difference in
charge, and so a voltage exists across the membrane. The left side of the container is
positively charged because some chloride ions have migrated, leaving a preponderance
of positive (Na") charges. The right side of the container is negatively charged because
some chloride ions (Cl!) have entered that chamber where no ions were before. The
charge is highest on the surface of the membrane, the area at which positive and negative
ions accumulate, and is much the same as what happens in a real cell.
120 ! CHAPTER 4
+
+
– ++
– –
–
–
+
+
+
– ++
– –
–
–
+
–
–
–
–
–
–
–
–
–
–
+
+
+
+
+
+
+
+
+
+
–
– –
–
–
–
–
– –
–
+
+ +
+
+
+
+
+ +
+
–
–
–
–
–
–
–
–
–
–
+ +
+
+
+
+
+
+
+
+
–
–
–
–
–
–
–
–
–
–
+ +
+
+
+
+
+
+
+
+ Time
(B)
Time Time
Cell membrane
(A)
Salt (NaCl)
Figure 4-9
Modeling the Cell Membrane
(A) Impermeable membrane. When salt
dissolves in water, positive and negative
ions diffuse but cannot cross the solid
barrier. (B) Semipermeable membrane. If
the barrier has a hole through which Cl!
can pass but Na" cannot pass, half of the
container will become positively charged
and the other half negatively charged.
The voltage difference will be greatest
across the membrane.
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