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Classical Conditioning
ROBERT E. CLARK
University of California, San Diego
I. Introduction
unconditioned responses do not show much habituation. In other
words, repeated presentations of the unconditioned stimulus will
continue to induce unconditioned responses. Alpha responses
quickly habituate, which means that after a few presentations of
the conditioned stimulus, they no longer occur. Ideally, conditioned
stimuli are chosen because they are neutral (i.e., do not initially elicit
a response). However, sometimes it is preferable to use a particular
conditioned stimulus even if it temporarily results in alpha responses.
II. Brief History
III. The Distinction between Classical and Instrumental/
Operant Conditioning
IV. Origin of the Term Classical Conditioning
V. Types of Classical Conditioning
VI. Acquisition of the CR
amplitude The magnitude of the conditioned response or unconditioned response. For example, in eyeblink conditioning the
amplitude is expressed as the distance the eyelid moves in
millimeters. Accordingly, a conditioned response of 2 mm has a
greater amplitude than a conditioned response of only 1 mm.
VII. Eyeblink Classical Conditioning in Humans
VIII. Problems for Studies of Human Eyeblink
Classical Conditioning
IX. The Emergence of Animal Studies
of Classical Conditioning
conditioned response A learned response that is elicited by the
conditioned stimulus.
X. Eyeblink Classical Condition as a Tool to Study
Brain Function
conditioned stimulus A stimulus that signals the unconditioned
stimulus. Initially the conditioned stimulus does not cause a
response, but eventually it elicits a conditioned response.
XI. The Search for the Engram
conditioned stimulus-alone test trial A conditioned stimulusalone test trial is a trial in which the unconditioned stimulus is
omitted, leaving only the conditioned stimulus presentation.
Conditioned stimulus-alone test trials are sometimes used because
the presentation of the unconditioned stimulus and subsequent
unconditioned response can obscure or mask the conditioned
response.
XII. The Brain Substrates of the Classically Conditioned
NM Response in the Rabbit
XIII. The Hippocampus Is Required for Trace Classical
NM Conditioning
XIV. The Amygdala Is Essential for the Acquisition and
Retention of the Classically Conditioned Fear Response
extinction training Extinction training can be presented following
the acquisition of the conditioned response. Conditioned responses
are formed by pairing a conditioned stimulus and an unconditioned
stimulus. During extinction training only the conditioned stimulus is
presented (i.e., the unconditioned stimulus is omitted). Extinction
training will gradually result in the disappearance of the conditioned
response. This is referred to as extinction ‘‘training’’ because the
conditioned response is not forgotten but inhibited. In other words,
extinction is an active process. Evidence that extinction training is
different from forgetting comes from paired conditioned stimulus
and unconditioned stimulus trials. This results in the rapid
reinstatement of the conditioned response. The reinstatement occurs
much more rapidly than the original acquisition of the conditioned
XV. Brain Structures Involved in Human
Classical Conditioning
GLOSSARY
alpha responses Nonassociative responses that follow the presentation of the conditioned stimulus. They are nonassociative in the
same way that unconditioned responses are nonassociative in that
they are innate reflexes to the presentation of a stimulus. However,
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Volume 1
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Copyright 2002, Elsevier Science (USA).
All rights reserved.
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CLASSICAL CONDITIONING
response. Therefore, the conditioned response is not forgotten but,
rather, inhibited.
interstimulus interval Sometimes called the conditioned stimulus–unconditioned stimulus interval, the interstimulus interval is the
amount of time between the onset of the conditioned stimulus and
the onset of the unconditioned stimulus.
intertrial interval A classical conditioning trial begins with the
onset of the conditioned stimulus and ends with the offset of the
unconditioned stimulus. The intertrial interval is the amount of time
between each individual trial and is usually an average amount of
time. The exact time between trials is usually varied within a
restricted range in order to prevent ‘‘time’’ from becoming a
conditioned stimulus as it is in temporal conditioning.
latency The amount of time between one event and another event.
For example, the latency of the conditioned response is the amount
of time between the onset of the conditioned stimulus and the onset
of the conditioned response. The latency of the unconditioned
response is the time between the onset of the unconditioned stimulus
and the onset of the unconditioned response.
pseudoconditioning Classical conditioning results in conditioned
responses when an association forms between the conditioned
stimulus and the unconditioned stimulus. However, sometimes
responses that appear to be conditioned responses, in that they
follow the presentation of a conditioned stimulus, result from
experience with the unconditioned stimulus only and not because of
an association between the conditioned stimulus and the unconditioned stimulus. This is known as pseudoconditioning.
spontaneous recovery Spontaneous recovery is related to the
process of extinction. Extinction training will result in the
disappearance of the conditioned response. However, when
the subject is given further extinction training following a break,
the conditioned response will initially reemerge or spontaneously
recover. Continued extinction training will more quickly result in the
disappearance of the conditioned response until spontaneous
recovery no longer occurs.
unconditioned response An innate response that is elicited by the
unconditioned stimulus.
unconditioned stimulus A stimulus that is signaled by the
conditioned stimulus. The unconditioned stimulus always elicits an
unconditioned response.
unconditioned stimulus-alone test trial In unconditioned stimulus-alone test trials, the conditioned stimulus is omitted, leaving
only the unconditioned stimulus presentation. In many classical
conditioning experiments, the amplitude of the unconditioned
response is an important measure (e.g., as a test to evaluate if a
manipulation such as a brain lesion affects the ability of the subject to
make a completely normal response). However, in a subject that is
emitting conditioned responses, it is not possible to obtain an
accurate measure of the unconditioned response amplitude because
of contamination from the presence of conditioned responses.
Unconditioned stimulus-alone test trials allow an uncontaminated
measure of unconditioned response amplitude in subjects that are
emitting conditioned responses.
Classical conditioning is a basic form of associative learning
in which the organism learns something about the
causal fabric of the environment or, in an experimental
setting, the relationship of stimuli. Stimuli can be
arranged so that one stimulus provides the organism
with information concerning the occurrence of another stimulus. This type of associative learning is
most commonly referred to as classical conditioning,
but it has also been termed Pavlovian conditioning,
respondent conditioning, and conditioned reflex type I
conditioning, or type S conditioning.
I. INTRODUCTION
In the most basic form of classical conditioning, the
stimulus that predicts the occurrence of another
stimulus is termed the conditioned stimulus (CS).
The predicted stimulus is termed the unconditioned
stimulus (US). The CS is a relatively neutral stimulus
that can be detected by the organism but does not
initially induce a reliable behavioral response. The US
is a stimulus that can reliably induce a measurable
response from the first presentation. The response that
is elicited by the presentation of the US is termed the
unconditioned response (UR). The term ‘‘unconditioned’’ is used to indicate that the response is ‘‘not
learned’’ but, rather, it is an innate or reflexive
response to the US. With repeated presentations of
the CS followed by US (referred to as paired training)
the CS begins to elicit a conditioned response (CR).
Here, the term ‘‘conditioned’’ is used to indicate that
the response is ‘‘learned.’’
The most well-known example of classical conditioning comes from the pioneering work of Ivan
Pavlov (1849–1936) and his dogs. In this prototypical
example, a bell (in reality the CS was usually a
metronome or buzzer) is rung just before meat powder
is placed on the dog’s tongue. The meat powder causes
the dog to salivate. Therefore, the meat powder acts as
the US, and the salivation caused by the meat powder
is the UR. Initially, the ringing bell, which serves as the
CS, does not cause any salivation. With repeated
pairings of the ringing bell CS and the meat powder
US, the ringing bell CS causes the salivation to occur
before the presentation of the meat powder US or even
if the meat powder not presented. The salivation in
response to the presentation of the ringing bell CS is
the learned or conditioned response.
II. BRIEF HISTORY
In 1904, Ivan Pavlov was awarded the Nobel prize in
medicine for his pioneering work on the physiology of
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digestion. Pavlov primarily studied the process of
digestion in dogs. This early research set the stage for
the discovery of a learning process that would come to
be known as classical conditioning. As early as 1880,
Pavlov observed that sham feedings, in which food was
eaten but failed to reach the stomach (being lost
through a surgically implanted esophageal fistula),
produced gastric secretions, just like real food did. He
immediately understood that this phenomenon must
involve the central nervous system and began a
program to thoroughly evaluate the parametric features of this learned response.
Pavlov modified his preparation in order to simplify
the forthcoming studies. Rather than measure gastric
secretions, he began measuring salivation. The first of
these studies involved showing the dog a piece of bread
as the CS. Pavlov then noticed that in dogs with
extensive training, even the act of an experimenter
walking into a room could elicit salivation. This
finding led to the discovery that a variety of stimuli
could induce salivation if paired with meat powder.
Accordingly, in a further simplification of his experimental procedures he began using the sound of a bell
presented with the meat powder to elicit salivation. It is
this preparation that has become synonymous with
Pavlov and historical examples of classical conditioning. In fact, Pavlov has become synonymous with
classical conditioning because the term Pavlovian
conditioning can be used interchangeably with classical conditioning.
Initially, Pavlov referred to the conditioned response as a ‘‘psychic secretion’’ to distinguish this type
of response from the unlearned physiological secretions that would later come to be known as the
unconditioned response. In 1903, a student of Pavlov’s
published a paper that changed the term psychic
secretion to conditioned reflex. The terms conditioned
reflex and unconditioned reflex were used during the
first two decades of the 20th century, during which
time this type of learning was often referred to as
‘‘reflexology.’’
Although Pavlov is correctly credited with the
discovery of classical conditioning, and with identifying and describing almost all the basic phenomena
associated with this form of conditioning, it is worth
noting that the phenomenon of classical conditioning
was independently discovered by an American graduate student in 1902. Edwin B. Twitmyer made this
discovery while finishing his dissertation work on the
‘‘knee-jerk’’ reflex. When the Patellar tendon is lightly
tapped with a doctor’s hammer, it results in the wellknown knee-jerk reflex. Twitmyer’s work required
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many tap-induced reflexes for each subject. Twitmyer,
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like Pavlov, noticed
that eventually the mere sight of
the doctor’s hammer (the CS) could produce a kneejerk reflex (the CR). This largely forgotten report was
the first example of classical conditioning of a muscle
reflex. The potential significance of this finding was not
apparent to Twitmyer, and the work was never
extended or cast in a theoretical framework as Pavlov
had done.
Pavlov’s work on classical conditioning was essentially unknown in the United States until 1906 when his
lecture ‘‘The Scientific Investigation of the Psychical
Faculties or Processes in the Higher Animals’’ was
published in the journal Science. In 1909, Robert
Yerkes, who would later become president of the
American Psychological Association, and Sergius
Morgulis published a thorough review of the methods
and results obtained by Pavlov. Although these reports
provided a true flavor of the potential value of classical
conditioning, the method was not immediately embraced by psychologists. This changed when John B.
Watson, who is widely regarded as the founder of a
branch of psychology known as behaviorism, championed the use of classical conditioning as a research
tool for psychological investigations. Watson’s presidential address delivered in 1915 to the American
Psychological Association was titled ‘‘The Place of the
Conditioned Reflex in Psychology.’’ Watson was
highly influential in the rapid incorporation of classical
conditioning, as well as other forms of conditioning,
into American psychology. In 1920, his work with
classical conditioning culminated in the now infamous
case of ‘‘little Albert.’’
Albert B. was an 11-month-old boy who had no
natural fear of white rats. Watson and Rosalie Rayner
used the white rat as a CS. The US was a loud
noise that always upset the child. By pairing the white
rat and the loud noise, Albert began to cry and
show fear of the white ratFa CR. With successive
training sessions over the course of several months,
Watson and Rayner were able to demonstrate that this
fear of white rats generalized to other furry objects.
The plan had been to then systemically remove this
fear using methods that Pavlov had shown would
eliminate or extinguish the CRFin this case, fear of
furry white objects. Unfortunately, little Albert,
as he as historically come to be known, was removed
from the study by his mother on the day these
procedures were to begin. There is no known reliable
account of how this experiment on classical conditioning of fear ultimately affected Albert B. Nevertheless,
this example of classical conditioning may be the
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most famous single case in the literature on classical
conditioning.
In 1921, a popular textbook on conditioning
changed the terms of conditioned and unconditioned
reflex to the current terms of conditioned and unconditioned response. This broadened the concept of
conditioning to include other behaviors that were not
merely automatic reflexes. In 1927, the Anrep (a
former student of Pavlov’s) translation of Pavlov’s
Conditioned Reflexes was published, thus making all of
his work available in English for the first time. The
availability of 25 years worth of Pavlov’s research, in
vivid detail, led to increased interest in the experimental examination of classical conditioningFan
interest that has continued to this day.
III. THE DISTINCTION BETWEEN CLASSICAL
AND INSTRUMENTAL/OPERANT CONDITIONING
In classical conditioning, no contingency exists between the CR and the presentation or omission of the
US. In other words, it does not matter if a CR is made
or not; the presentation of the US still occurs and is
experienced and processed by the subject. This has
been termed stimulus-contingent reinforcement or the
law of contiguity. In instrumental conditioning, in
contrast, a contingent relationship is arranged between
the subject’s response and the presentation or nonpresentation of a reinforcer. In other words, instrumental conditioning involves response-contingent
reinforcement or the law of effect.
The simplest forms of learning are known as
nonassociative learning. Examples of nonassociative
learning include habituation (a decrease in a response
to repeated presentations of a stimulus) and sensitization (an increase in a response to repeated presentation
of a stimulus). Associative learning is a more complex
form of learning. Classical conditioning and instrumental conditioning are both examples of associative
learning. In classical conditioning, an association is
made between two stimuli, the CS and US. This
association is manifested by the occurrence of a
conditioned response. In instrumental conditioning,
an association is made between a stimulus and the
outcome of a response. In other words, the organism
learns what responses are reinforced given a particular
stimulus. Although classical conditioning and instrumental conditioning are both examples of associative
learning, classical conditioning is generally viewed as
the simpler form of learning. There are many reasons
for considering classical condition to be a simpler form
of learning. For example, classical conditioning has
been demonstrated in organisms that are very low on
the phylogenetic scale, such as planaria, slugs, and
leeches. Second, the ability to be classically conditioned appears earlier ontogenetically than the ability
to be instrumental conditioned. Successful classical
conditioning has been reported for chick embryos,
neonatal monkeys, goats, and dogs as well as human
fetuses in utero.
IV. ORIGIN OF THE TERM
CLASSICAL CONDITIONING
Often, it is possible to precisely identify the time and
reason a new scientific term is introduced. Generally,
this is possible because the author of the new term
describes the reasons for introducing the term and
justifies why the particular term was chosen. For
example, the term instrumental conditioning was
coined by Clark L. Hull to describe the type of
learning in which the subject is ‘‘instrumental’’ in
obtaining reinforcement. That is, the animal is the
instrument, as in maze learning. Operant conditioning
was chosen by B. F. Skinner because the subject must
perform a behavioral ‘‘operation’’ to obtain reinforcement. In other words, the animal operates on a
manipulandum in the environment, such as pressing
a bar to obtain food. However, unlike instrumental
and operant conditioning, there does not appear to be
an instance in which a single individual coined the term
classical conditioning. Therefore, only an inference
can be made concerning the origin of the term classical
conditioning.
Only in the most rare cases do authors comment on
the origin of the term classical conditioning. Often in
these cases, the term is inaccurately attributed to John
B. Watson. This is understandable because Watson
was largely responsible for publicizing the classical
conditioning method and outlining how it could be
used as a method of scientific investigation. However,
Watson never actually used the term classical conditioning, instead referring to it as simply the ‘‘conditioned reflex.’’ His 1930 edition of Behaviorism was his
last significant scientific publication, and although the
process of classical conditioning is referenced extensively, the term was never used.
Before the 1940s, the process of classical conditioning was referred to most often as the conditioned
reflex, Pavlovian conditioning, or simply conditioning.
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However, in the 1930s, scientists began to understand
that the laws governing learning, in paradigms in
which reinforcement was contingent on the organism’s
behavior, appeared to be fundamentally different from
the laws governing the conditioned reflex. The latter
type of learning would come be known as instrumental
or operant conditioning. This created a need to
distinguish these different forms of conditioning. It is
my contention that the term classical conditioning
developed as a contraction of the descriptive phase
‘‘classical Pavlovian conditioning’’ that was used to
denote the ‘‘well-known’’ (i.e., classical) type of
conditioning used by Pavlov (i.e., Pavlovian).
V. TYPES OF CLASSICAL CONDITIONING
Classical conditioning is a generic term that can refer
to a variety of different types of classical conditioning
procedures and paradigms. Two different parameters
can distinguish the type of classical conditioning: (i)
the temporal arrangement and spacing of the CS and
the US and (ii) the type of response that is measured
and conditioned. Some general comments regarding
the influence that different types of conditioning have
on behavior can be made, but it is impossible to make
any specific comments regarding conditioning. The
specifics depend on the response system being measured, the nature of the stimuli being used, and the
species being conditioned.
A. Temporal Arrangement and Spacing of the CS
and the US
The relationship of the CS and the US can be arranged
in different ways to produce different conditioning
paradigms. These arrangements can greatly influence
how the CR develops. Figure 1 illustrates the major
classical conditioning paradigms. The upward movement of a line represents the onset of a stimulus, and
the downward movement of a line represents the offset
of a stimulus.
1. Simultaneous Conditioning
In simultaneous conditioning the CS and the US are
presented simultaneously. In this case, because the US
always elicits a UR and the CS and US are presented
together, it is not possible to determine if CRs are
present. In order to determine if a CR has developed, a
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Figure 1
Temporal arrangements of the CS and the US (top trace)
used in five classical conditioning paradigms. The upward movement
of a line represents the onset of a stimulus, and the downward
movement of a line represents the offset of a stimulus. A,
simultaneous conditioning; B, delay conditioning; C, trace conditioning; D, backward conditioning; E, temporal conditioning. In
the case of temporal conditioning, there is no discrete CS. The
interval of time between the USs serves as the CS.
CS-alone trial must be presented (i.e., the US is
omitted). If the CS elicits a response on the CS-alone
trial, this response is a CR. This form of conditioning is
not commonly used, and it generally yields only weak
conditioning, if any at all.
2. Delay Conditioning
In delay conditioning, the CS onset precedes the US
onset. The termination of the CS occurs with the US
onset, during the US, at the termination of the US, or
at some point after the US. This paradigm is called
delay conditioning because the onset of the US is
delayed relative to the onset of the CS. Generally,
responses that develop to the CS and occur before the
onset of the US are CRs. This is the most common
conditioning paradigm and generally results in the
most robust and rapid conditioning.
3. Trace Conditioning
In trace conditioning, the CS is presented and terminated before the onset of the US. The interval
separating the CS offset and the US onset is called
the trace interval. This paradigm was named trace
conditioning by Pavlov because in order for conditioning to occur, the subject (i.e., the subject’s brain)
must maintain a memory ‘‘trace’’ of the CS. Responses
that develop in response to the CS and occur before the
onset of the US are CRs. This form of conditioning is
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also common and yields good conditioning but
generally not as readily as delay conditioning.
4. Backward Conditioning
In the backward conditioning paradigm, the US is
presented and terminated prior to the CS. A CR is a
response that follows the presentation of the CS. This
form of conditioning is not commonly used and in
most circumstances does not result in conditioning.
However, in some situations backward conditioning
can occur.
5. Temporal Conditioning
In temporal conditioning there are no discrete CSs.
Instead, the US is presented at regular intervals, and
over time the CR will be exhibited just prior to the
onset of the US. In this case, the CS is the time interval.
Temporal conditioning is possible in some experimental paradigms, but in most classical conditioning
paradigms it does not result in conditioning.
6. Differential Conditioning
unpaired training is used to describe a situation in
which the CS and the US never coincide. Random
unpaired training is used to describe a situation in
which the CS and the US rarely coincide but occasionally (i.e., by chance) do so. Random unpaired
training is generally thought to be superior to explicitly
unpaired training because during explicitly unpaired
training the animal learns that the CS signals a safety
period (i.e., the US will not occur).
Because the CS and the US are never paired, an
association between them cannot be made. If responses nevertheless follow the presentation of the CS,
it can be concluded that pseudoconditioning has
occurred and not classical conditioning. If unpaired
presentations do not result in responses to the CS, then
any responses that subsequently develop in response to
the CS, after paired training is begun, can be considered true CRs.
B. Types of Classical Conditioning Based on the
Measured Response
In differential conditioning, two CSs are used. One of
the CSs always precedes and predicts the US. This CS
is termed the positive CS or the CS+. The other CS is
not predictive of the US and occurs alone. This CS is
termed the negative CS or the CS. Differential
conditioning is indicated by a greater number of CRs
in response to the CS+ than to the CS.
In addition to the conditioning paradigms discussed
previously, different types of classical conditioning can
be characterized by the measured response. For
example, in Pavlov’s experiments, he measured salivation, whereas in Twitmyer’s experiments, he measured
the knee-jerk response. Although both of these basic
experiments are examples of classical conditioning,
they involve different response systems.
7. Controls for Pseudoconditioning
1. Two Fundamental Response Classes
Classical conditioning results in CRs when an association forms between the CS and the US. However,
sometimes responses that appear to be CRs, in that
they follow the presentation of a CS, result from
experience with US only and not because of an
association between the CS and the US. This is known
as pseudoconditioning. For example, if a very intense
US is presented (e.g., a strong shock), the organism
might respond to any subsequent stimulus presentation. The response does not occur because of an
association between the CS and the US but, rather,
because the US sensitizes the subject, making it more
likely to respond to any stimulus presentation. To test
for the possibility of pseudoconditioning, the CS and
the US can be arranged so that the CS does not predict
the US. This is known as unpaired training. There are
two basic forms of unpaired training. Explicitly
The nervous system can be divided into the central
nervous system (CNS) and the peripheral nervous
system (PNS). The CNS consists of all the neural tissue
that is encased in bone (i.e., the brain and spinal cord).
The CNS is discussed later. Because this section
focuses on responses, the PNS will be discussed. In
order for a response to occur, the PNS must be engaged
(excluding responses of neurons that can be recorded
from the CNS). The PNS can be divided into the
autonomic nervous system and the somatic nervous
system. The autonomic nervous system controls the
viscera, and the somatic nervous system controls
muscles.
a. Autonomic Classical Conditioning Autonomic
classical conditioning refers to any classical conditioning paradigm in which the measured response is under
CLASSICAL CONDITIONING
the control of the autonomic nervous system. The
autonomic nervous system consists of two divisions,
the sympathetic nervous system and the parasympathetic nervous systems. These two systems work
together, in opposing directions, to control bodily
functions such as heart rate, breathing, dilation and
constriction of the pupil, and the control of sweat
glands. These systems are not generally under voluntary control but can be modified by classical conditioning. Autonomic conditioning has been used
extensively because in addition to involving primarily
involuntary responses, autonomic responses can also
be used as an index of changes in emotion. Autonomic
conditioning is sometimes referred to as conditioned
emotional responses because changes in emotion are
accompanied by changes in these autonomic measures.
For example, many of these measures are also used in
polygraph/lie-detection work. The following is a brief
overview of the most common types of autonomic
conditioning studies.
i. Galvanic Skin Response/Skin Conductance Response Conditioning This response is measured by the
change in skin resistance to an electrical current.
Research using this response measure dates back to the
1880s. For most of this time, the response was termed
the Galvanic skin response (GSR) in honor of Luigi
Galvani (1737–1798), an early pioneer in research
describing the electrical nature of the body. Today,
descriptive terms are commonly used, such as the
electrodermal response or the skin conductance
response (SCR). This response is measured by passing
a small amount of electrical current between two
electrodes pasted to the skin. The conductance (the
reciprocal of resistance) between the two electrodes is
measured. Many different stimuli can induce a SCR.
For example, a mild shock, or any new stimulus of
sufficient intensity as to attract the attention of the
subject, can cause an autonomic response in which
sweat glands pump extra sweat into sweat ducts
located in the skin. The net effect of this action is an
increase in skin conductance (i.e., a skin conductance
response). In conditioning experiments in which, for
example, a tone CS is paired with a shock or loud noise
US, an association is made between the CS and the US
and the CS begins to elicit a classically conditioned
SCR.
ii. Heart Rate Conditioning Another common
autonomic conditioning paradigm is the classically
conditioned heart rate response. In this paradigm the
change in heart rate (i.e., heartbeats per minute) is
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measured with electrodes pasted on the chest. For
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example, a tone CS
can be paired with a mild shock
US. Initially, the CS does not cause a change in the
heart rate, but the shock will increase the heart rate.
With continued pairing of the CS and the US, the CS
will elicit a CRFa change in heart rate. Interestingly,
the CR in this case is change in heart rate to the CS, but
the direction of change (i.e., slower or faster) depends
on the animal species being testing. For example, the
CR with human subjects is an increase in heart rate,
which is called conditioned tachycardia (heart rate
increasing). However, the CR with, for example,
rabbits, is a decrease in heart rate, which is called
conditioned bradycardia (heart rate slowing).
iii. Other Examples Another example of autonomic classical conditioning is the conditioned pupillary response, which is a conditioned change in the size
of the pupil. This response was first conditioned in
1922, but today it is rarely used because it is a difficult
response to condition and to measure, and it is subject
to a great deal of noise (i.e., spontaneous responses
that are unrelated to the CS or the US). As noted
previously, salivary conditioning was used by Pavlov
in the initial demonstration of classical conditioning
and this response was adapted for work with humans
by Karl Lashley (1890–1958). Today, this paradigm is
almost never used because salivation is a relatively
slow response, difficult to measure, and difficult to
condition in humans.
b. Somatic Classical Conditioning Somatic classical conditioning refers to any classical conditioning
paradigm in which the measured response is under the
control of the somatic nervous system. The somatic
nervous system as it relates to classical conditioning
controls striate or skeletal muscles. Accordingly, any
response that requires a motor movement must be
controlled by striate muscles and the somatic nervous
system. The following is a brief overview of the most
common types of somatic conditioning paradigms.
i. Eyeblink Classical Conditioning Eyeblink classical conditioning is by far the most common form of
experimental conditioning paradigm with both humans and experimental animals. As early as 1922,
eyeblink classical conditioning paradigms were being
used. In eyeblink conditioning a CS (typically a tone or
light) is paired with a US (e.g., a mild shock or puff of
air to the eye). Eyeblink studies have been carried out
in a variety of species, including humans, monkeys,
rabbits, cats, rats, and mice. The response can be
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measured with a minitorque potentiometer. A string is
attached to the eyelid and any eyelid movement
changes the resistance in the potentiometer, which
can then be recorded. Electromyographic (EMG)
measures can also be used to record the activity of
the muscles controlling the eyeblink. Today, the most
common method of measuring eyeblink responses in
humans is the use of an infrared reflective sensor. In
this method, an infrared beam is directed at the eye
(usually mounted in goggles) and the amount of light
reflected by the eyelid is recorded. Eyeblinks change
the amount of light that is reflected and subsequently
detected by an infrared sensor.
ii. Nictitating Membrane Classical Conditioning
Closely related to eyeblink conditioning, conditioning
of the nictitating membrane (NM) is the most
frequently used response measure in rabbits, which
are the most frequently used experimental subjects for
conditioning studies. The NM is often called the ‘‘third
eyelid’’ and it consists of a sheet of cartilage located
behind the inner canthus of the eye. When the eyeball is
stimulated, the eyeball retracts into the eye socket. This
causes the NM to passively sweep across a portion of
the eyeball. The NM response is popular because it is
simple to measure (usually with a minitorque potentiometer) and because the NM cannot completely cover
the eye. Thus, it prevents the subject from avoiding the
airpuff US (the eyelids are prevented from closing by
the experimenter during NM conditioning).
iii. Leg Flexion Classical Conditioning In the
typical leg flexion experiment, an animal is usually
restrained so that the legs hang freely, although it has
also been used in freely moving subjects. A CS is paired
with a mild shock US to the leg, which causes the leg to
flex. With pairing of the CS and the US, a CR develops
where the leg flexes in response to the CS. The response
can be measured by a minitorque potentiometer or
EMG.
iv. Fear Classical Conditioning Classical conditioning has been increasingly used to study the learning
of fear. This paradigm can be considered a hybrid of
autonomic and somatic classical conditioning because
fear causes numerous autonomic changes, which could
be measured as the CR. However, in the rat, the most
common subject for studies of this type, fear can also
be measured with the somatic response of freezing. In
the typical paradigm, a tone CS is paired with a shock
US. The shock US is delivered to the rat through an
electrified floor grid. With pairing of the CS and the
US, a fear CR develops in response to the CS. In this
case, the fear CR is freezing (the rat holds completely
still).
VI. ACQUISITION OF THE CR
As noted previously, the specifics regarding any aspect
of classical conditioning must be reserved for the
particular type of classical conditioning paradigm, the
response that is measured, and the species that is used.
However, some general features can be noted regarding the acquisition of the CR. The most fundamental
element of classical conditioning is the association of
the CS and the US that results in the acquisition of the
CR. During the initial presentation of the CS and the
US, no response to the CS is observed. With continued
pairing of the CS and the US (i.e., presentation of
additional training trials), CRs begin to develop in
response to the CS. This development of the CR is
referred to as the acquisition of the CR. It is often
referred to as an increasing probability of CRs. In
other words, with continued training, the probability
of a CR on a given trial increases. In some conditioning
paradigms (such as classical conditioning of the NM
response in rabbits) this probability can approach 0.99
(i.e., CRs on almost every trial). During the early
phases of CR acquisition, CRs are generally smallamplitude responses that gradually (over the course of
training) grow larger until they become as large as the
UR. The latency of the CR also tends to change during
CR acquisition. Initially, the latency of the CR onset
begins just before the onset of the US. With continued
training the latency decreases so that the onset of the
CR begins well before the onset of the US. Finally, the
CR is acquired to the extent that the maximum
amplitude of the CR (the CR peak) occurs at the time
of the US onset. This is sometimes referred to as a
‘‘well-timed’’ CR.
A. Factors That Can Influence the Acquisition
of the CR
1. Interstimulus Interval
Every type of conditioning paradigm has an optimal
interstimulus interval (ISI). The optimal ISI depends
on the particular paradigm, but it is clear that ISIs that
are very short or very long and result in little or no CR
acquisition. For example, in the rabbit classically
conditioned NM response paradigm, the optimal ISI
CLASSICAL CONDITIONING
for delay conditioning is 250 msec. An ISI of 100 msec
or less results in poor conditioning, as does increasing
the ISI to longer than 250 msec. In this paradigm, an
ISI of 2000 msec (i.e., 2 sec) will not result in any CR
acquisition.
2. Intertrial Interval
It is a general finding from many conditioning
paradigms that increasing the ITI will tend to produce
more rapid CR acquisition, although this influence is
not robust in most cases. Reducing the ITI to less than
several seconds can drastically impair acquisition of
the CR. The typical ITI ranges from 30 to 60 sec.
3. Temporal Arrangement and Spacing of the CS
and the US
As noted previously, delay conditioning generally
results in the most rapid rate of CR acquisition
followed by trace conditioning. Simultaneous conditioning generally results in much poorer CR acquisition. In many cases simultaneous conditioning (ISI¼0)
does not produce CRs. Backward conditioning results
in CRs in only a few paradigms and generally does not
produce any CR acquisition.
4. CS Intensity
It was initially believed that the CS intensity did not
influence that rate of CR acquisition, but recent studies
indicate that more intense CSs tend to result in slightly
more rapid CR acquisition.
5. US Intensity
An increase in the acquisition rate of the CR has been
a consistent finding with increases in the intensity of
the US.
VII. EYEBLINK CLASSICAL CONDITIONING
IN HUMANS
It was previously noted that different types of classical
conditioning paradigms can be distinguished on the
basis of the measures response. By the early 1930s,
successful classical conditioning had been reported in
23 different response systems (e.g., eyeblink response,
skin conductance response, pupillary response, leg
flexion response, and salivary response). Of these
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numerous preparations, the majority were explored
BrainSoft.ir
for only short periods
before being, for the most part,
abandoned for one reason or another. For example,
the salivary preparation in humans or other experimental animals never flourished because of many
methodological difficulties.
Classical conditioning of the skin conductance
response has had a long history dating back to the
late 19th century. However, skin conductance conditioning failed to flourish in the 1930s–1950s because
the physiological basis of the response was poorly
understood and difficult to measure accurately with
the equipment of the day. A renewed interest occurred
in the 1960s due to a better understanding of the
physiology of the response and better and more readily
available equipment for measuring and quantifying
the response. Today, this paradigm still enjoys some
popularity with researchers studying cognitive factors
of classical conditioning and the neural mechanism
underlying conditioned emotional responses.
By the 1940s the human eyeblink classical conditioning paradigm had surpassed all other conditioning
paradigms in terms of number of articles published
primarily because it was methodologically superior to
all other classical conditioning paradigms. From the
1940s through the 1960s, studies of human eyeblink
conditioning remained the dominant paradigm for
studying the processes and variables that related to
classical conditioning. During this time, methodological improvements that included precise measurement
of the eyeblink response allowed investigators to
explore the effects of such variables as the intertrial
interval, interstimulus interval, CS intensity, US
intensity, and variable reinforcement schedules. Additionally, cognitive factors were also extensively
explored. For example, subjects were asked about the
information they acquired during the conditioning
session. This information was then compared to how
well the subjects acquired the CR. Other studies
explored how instruction sets affected CR acquisition
rates: that is, how different verbal instructions given to
subjects before conditioning affected CR acquisition
rates.
VIII. PROBLEMS FOR STUDIES OF HUMAN
EYEBLINK CLASSICAL CONDITIONING
In all forms of classical conditioning, the responses are
considered primarily reflexive in nature. For example,
the UR is an innate, automatic, ‘‘reflexive’’ reaction to
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CLASSICAL CONDITIONING
the puff of air that is delivered to the eye. With repeated
pairing of a CS and a US a learned, conditioned
response develops. This response is also thought to be
reflexive and, as such, should not require cognitive
involvement. Nevertheless, although an eyeblink response can be involuntary, clearly the eyeblink
response can also be brought under voluntary control.
If individuals become aware of the fact that the CS
predicts the US, they are in a position to voluntarily
blink their eyes to avoid the airpuff (i.e., blink on
purpose). This circumstance has caused concern
among experimentalists because it has been argued,
at least since the 1940s, that the processes and
characteristics of responses that are voluntary are
very different from those that are involuntary or
reflexive. That is, classical conditioning measures
involuntary, automatic responses, not purposeful
behavior. Therefore, some means of identifying voluntary responses needed to be developed so that they
could either be discarded as contaminants or analyzed
separately.
Two criteria emerged for identifying voluntary
responses. The first was based on the slope of the
response. Voluntary responses were believed to be
more rapid and thus to have a characteristically steeper
slope than a true CR. The second was based on
response latency. Voluntary responses were believed to
have a short onset latency (which also involved a steep
slope), and eye closure was maintained until the onset
of the US. Despite these improvements, there is no
consensus about the most appropriate methods for
detecting voluntary responses. In fact, the only largescale study to test the validity of these two criteria
(slope and latency) found that neither was fully
satisfactory for discriminating voluntary responses
from conditioned responses.
By the 1960s, studies of human eyeblink classical
conditioning began to wane. This gradual decrease in
human eyeblink classical conditioning research was
likely due to a combination of at least two factors.
First, researchers were never completely successful in
identifying and dealing with the issue of voluntary vs
conditioned responding. Second, researchers never
reached a consensus on what the ‘‘standard’’ conditions should be for conditioning studies. Various
laboratories used different CS and US intensities,
different ISIs and ITIs, and different criterion for
determining if responses were CRs. Consequently,
there were persistent problems with obtaining reproducible results between different laboratories, which
essentially prevented progress in exploring interesting
variables.
IX. THE EMERGENCE OF ANIMAL STUDIES OF
CLASSICAL CONDITIONING
Although human eyeblink classical conditioning studies began a steep decline in the 1960s, classical
conditioning studies using animals showed rapid
growth. This was in part likely due to at least two
factors. First, some experimentalists moved from
human conditioning research to working with animals,
which served to stimulate the field of animal work.
Second, although problematic, the human research on
classical conditioning nevertheless revealed the potential of classical conditioning to serve as a paradigm for
the systematic and thorough analysis of associative
learning if it could be appropriately exploited. What
was needed was the development of a ‘‘model’’
paradigm of classical conditioning in which all the
basic features (e.g., CS and US types and intensities,
measurement of the responses, and ISIs and ITIs)
would be held consistent across laboratories. A model
paradigm must result in robust acquisition of the CR,
which is reliable across laboratories. This would allow
theoretical questions about learning and memory to be
addressed. Additionally, these methods must be economical and relatively easy to implement, and the
characteristics of the learned response must not be
unique to the experimental circumstances or to the
species being tested.
In the early 1960s, Isidore Gormezano and colleagues developed a paradigm in which classical conditioning of the NM response was used with rabbits. The
NM is vestigial in humans but is quite pronounced in
the rabbit. It consists of a sheet of cartilage located
behind the inner canthus of the eye. When the eyeball is
stimulated, it retracts into the eye socket. This causes
the NM to passively sweep across a portion of the
eyeball. This movement is the measured response. The
NM response was chosen because it is simple to
measure (usually with a minitorque potentiometer)
and because the NM cannot completely cover the eye.
In this preparation, the rabbit’s eyelids are held open
with clips to prevent the subject from completely
closing its eyelids and avoiding an airpuff US. Because
the rabbit cannot avoid the airpuff US, the response
cannot be an instrumental response but remains
squarely within the domain of classical conditioning.
This paradigm remains the model classical conditioning paradigm. It has endured because it has simply
proven to be an ideal paradigm. The result is that the
processes and factors that influence the acquisition of
the CR are now understood in detail. These details
CLASSICAL CONDITIONING
allow learning theories to be constructed. This model
system then allows the hypotheses that are derived
from these theories to be rigorously tested and
interpreted against an immense background of empirical data. In this respect, the importance of classical
conditioning to modern learning theory cannot be
overestimated.
X. EYEBLINK CLASSICAL CONDITION AS A
TOOL TO STUDY BRAIN FUNCTION
In his preface to the Russian edition of his 1927 book
Conditioned Reflexes, Ivan Pavlov wrote ‘‘At [this]
time [I am] am convinced that this method of research
[classical conditioning] is destined, in the hands of
other workers, and with new modifications in the mode
of experimentation, to play a yet more considerable
part in the study of the physiology of the nervous
system.’’ Pavlov’s statement can be viewed not only as
prophetic but also as in fact quite understated. Until
the past 25 years, Pavlov’s enthusiasm for classical
conditioning as a method of studying brain function
had not been shared by physiologists. As a research
procedure, classical conditioning had been almost the
exclusive property of psychologists. However, beginning in the mid-1970s, classical conditioning became
one of the most important tools for relating learning to
specific brain structures.
XI. THE SEARCH FOR THE ENGRAM
The term engram is a hypothetical construct used to
represent the physical processes and changes that
constitute memory in the brain, and the search for the
engram is the attempt to locate and identify that
memory. Karl Lashley was perhaps the first person to
clearly conceptualize the issue in a framework that
would lend itself to experimental analysis. Lashley’s
primary interest was in localizing the engram to a
specific region of the brainFan endeavor that would
prove to be extraordinarily difficult and ultimately end
in failure for Lashley. A likely reason why Lashley and
others have historically had such great difficulty in
locating an engram is because the behavior they
typically used was an operant form of conditioningFa
relatively complex form of associative learning. To
make localization more tractable a simpler behavior
was needed. Classical conditioning of the NM response in rabbits proved to be the solution.
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For many reasons, Classical conditioning is a
valuable tool forBrainSoft.ir
studying the physical processes of
the brain that may be important for forming and
storing memory. The presentation of the CS and the
US is determined by the experimenter, not by the
subject’s behavior. This has important implications for
the analysis of stimulus selection, which can be
precisely manipulated by the experimenter. However,
of greater importance is the fact that the CR is time
locked to the CS. This allows a temporal analysis of
neural events and then correlation of electrophysiological recordings with changes in the CR. The conditioning procedures provide a more adequate control
for nonspecific effects of training on biological processes than do operant procedures. For example, the
same kind of density of stimulation and number of
unconditioned responses can be produced in both
experimental and control conditions. Perhaps the
greatest advantage is that the effects of experimental
manipulations on ‘‘learning’’ rather than ‘‘performance’’ can be easily evaluated. This problem of
learning versus performance has plagued the study of
brain substrates of learning from the beginning. For
example, does a brain lesion impair a learned behavior
because it damages the memory trace or because it
impairs the animal’s ability to respond? This problem
can be circumvented by simply comparing the amplitude of the learned or conditioned response to the
reflex or unconditioned response amplitude. If the
lesion abolishes the CR (the learned response) but
leaves the UR (the ability to respond) intact, then it can
be concluded that the lesion has impaired learning
rather than performance.
The use of the classically conditioned NM response
in rabbits offers additional advantages for studying the
neural correlates of the learned behavior. Rabbits are
docile animals that do not find full-body restraint
aversive. They will usually sit quietly for more than 2 hr
with little or no struggling. Rabbits also have a very
low spontaneous blink rate, which reduces the amount
of contamination caused by blinks that are unrelated
to the CS and the US. The parametric features of the
CR have been well characterized. The behavioral NM
response is robust and discrete and the exact amplitude–time course of the response is easily measurable.
The CR is acquired, at least to a significant degree, in a
single training session, but not all at once. This allows
for an analysis of brain substrates over a period of time
as learning is proceeding (as opposed to one-trial
learning or some operant tasks, which show a rapidly
accelerating acquisition curve). The presentation of
the CS and the US does not yield sensitization or
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CLASSICAL CONDITIONING
pseudoconditioning. That is, unpaired presentations
of the CS and the US do not increase the ability of the
CS to elicit a response; they also do not increase the
spontaneous blink rate. These are the primary reasons
that led Richard F. Thompson and associates to
choose this paradigm to continue the search for the
elusive engram.
Conceptually, to search for an engram, a neural
circuit must be identified. No single neurobiological
method or technique is sufficient in and of itself to
define the characteristics of a neural circuit, including
the essential site of plasticity. Therefore, numerous
methods must be used to determine the roles that
different brain structures play in any learned behavior.
To date, the most fruitful methods have been electrophysiological recordings, permanent and reversible
lesions, and electrical microstimulation of various
nuclei and fiber tracts. These methods are used in
combination with classical conditioning and with the
assumption that there are neural pathways connecting
the CS, the US, and the UR pathways. It is also
assumed that it is possible to localize a specific brain
region where some essential modification takes place
to drive the conditioned response. All these methods
have been used successfully in defining the circuit for
classical eyeblink conditioning.
XII. THE BRAIN SUBSTRATES OF THE
CLASSICALLY CONDITIONED NM RESPONSE
IN THE RABBIT
Since the early 1970s, Thompson and many others
have used a variety of methods to search for the
classically conditioned NM response engram. A neuronal circuit diagram has been systematically constructed during the course of 20 years to represent all
the brain structures that are essential for the acquisition and retention of the classically conditioned NM
response for the delay conditioning paradigm. This
circuit is the most thoroughly investigated and completely understood learning and memory circuit
known for the mammalian brain. The essential site of
plasticity (i.e., the location of the engram) appears to
be the interpositus nucleus of the cerebellum, although
the cerebellar cortex is also important.
A. Components of the Circuit
Figure 2 is a neuronal circuit diagram that represents
all the brain components that are essential for the
acquisition and retention of the CR.
Figure 2 The cerebellar neural circuit for delay eyeblink/nictitating membrane (NM) classical conditioning. The focus of this diagram is on
the relationships between the conditioned stimulus (tone CS), unconditioned stimulus (airpuff US), conditioned response (CR), unconditioned
response (UR), and their connecting fiber pathways. The cerebellar cortex in the diagram consists of granule cells, parallel fibers, and Purkinje
cells. Cerebellar structures in the diagram include the cerebellar cortex and interpositus nucleus. All other structures depicted are located in the
brain stem. Pairing of the CS and US results in an essential plastic change in the interpositus nucleus that results in the generation of the CR.
CLASSICAL CONDITIONING
1. The CS Pathway
The tone CS is detected by auditory hair cells, which
stimulate spiral ganglion cells. These cells project to
the cochlear nucleus, which then projects to the lateral
pontine nuclei. The lateral pontine nuclei send mossy
fibers to both interpositus nucleus and granule cells in
the cerebellar cortex.
2. The US Pathway
The airpuff US is detected by similunar ganglion cells
that send somatosensory information to the spinal
trigeminal nucleus. This nucleus projects to the dorsal
accessory olive. The olive sends climbing fibers to both
the interpositus and the cerebellar cortex.
3. The UR Pathway
The sensory trigeminal projects to the abducens,
accessory abducens, and facial motor nucleus, which
are the motor nuclei that drive the eyeblink and NM
response.
4. The CR Pathway
The interpositus nucleus, which receives convergent
information concerning the CS and the US, projects to
the red nucleus. The red nucleus then projects to the
same motor nuclei that drive the eyeblink and NM
response (i.e., the abducens, accessory abducens, and
facial motor nucleus).
5. Circuit Philosophy and Function
Figure 2 focuses on the relationships of the CS, US,
CR, and UR pathways rather than emphasizing the
physical position of the nuclei and tracts within the
brain. Initially, in a naive subject, the CS does not
cause a NM response. The US stimulates the trigeminal nucleus, which then projects to motor nuclei to
cause the reflexive UR from the first trial on. During
training the interpositus nucleus receives convergent
CS and US information. Eventually, this convergent
information causes a change (i.e., learning) in the
interpositus nucleus and cerebellar cortex. This change
enables the CS information to activate the interpositus, which can then activate the red nucleus. The red
nucleus then activates the motor nuclei, which then
drive the NM response. This response occurs before
the delivery of the airpuff US. This is the conditioned
response.
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B. Brain Structures That Are Critical for Classical
BrainSoft.ir
Conditioning of the NM Response
1. Interpositus Nucleus
The interpositus nucleus receives convergent CS and
US information from the pontine nuclei (CS information) and the inferior olive (US information). The
plastic changes that occur in the interpositus as a result
of this convergent information are responsible for the
CR. The interpositus is considered to be the prime
location of the classically conditioned NM response
engram. Damage to the interpositus nucleus completely and permanently abolishes the CR without
affecting the UR.
2. Cerebellar Cortex
The cerebellar cortex also receives convergent CS and
US information. The output of the cerebellar cortex
goes through the interpositus nucleus. It has been
suggested that the cerebellar cortex might form and
store the essential plasticity for the engram and that
interpositus lesions only block the expression of the
CR. However, large lesions of the cerebellar cortex do
not abolish the CR or prevent the acquisition of the
CR. The cerebellar cortex likely plays a critical
modulatory role in the acquisition and expression of
the CR.
3. Pontine Nuclei
The pontine nuclei receive information about the tone
CS and relay this information to the interpositus
nucleus and cerebellar cortex. Rabbits can be classically conditioning by electrically stimulating the
pontine nuclei in place of a tone CS and pairing the
stimulation with an airpuff US.
4. Inferior Olive
The inferior olive receives US information from the
trigeminal nucleus located in the brain stem. The
inferior olive then relays this information to the
interpositus and cerebellar cortex. Rabbits can be
classically conditioned by electrically stimulating the
inferior olive in place of an airpuff US. Pairing a tone
CS with inferior olive stimulation as the US results in
the development of CRs. In fact, rabbits can be
conditioned without tones or airpuffs by stimulating
the pontine nuclei as the CS and the inferior olive as the
US. In well-trained rabbits (i.e., rabbits showing CRs),
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CLASSICAL CONDITIONING
lesions of the inferior olive result in a gradual
extinction of the CR as if the US has been removed,
even though the US is still being presented. This
indicates that the inferior olive sends critical US
information to the interpositus and cerebellar cortex.
5. Red Nucleus
The red nucleus is a critical structure in the CR
pathway. It receives input from the interpositus, which
is outputting a neural signal for driving the CR. The
red nucleus then relays this signal to motor nuclei for
driving the learned NM response. Lesions of the red
nucleus abolish the conditioned response. It is known,
however, that the red nucleus is not responsible for
forming the CR because reversibly inactivating the red
nucleus during training prevents the expression of the
CR but does not prevent the acquisition of the CR.
When the lesion is reversed (i.e., restored to normal
function), CRs rapidly appear. In contrast, when the
interpositus is inactivated, there is no acquisition of
the CR.
6. Trigeminal Nucleus
The trigeminal nucleus receives information regarding
the occurrence of the US. It then sends this information to the interpositus and cerebellar cortex (via the
inferior olive) so that an association between the CS
and the US can be accomplished. It also sends the US
signal to the motor nuclei for driving the UR.
7. Accessory Abducens
The accessory abducens is the motor nucleus that
drives the NM response. It receives information from
the trigeminal nucleus for driving the UR and
information from the red nucleus for driving the CR.
XIII. THE HIPPOCAMPUS IS REQUIRED FOR
TRACE CLASSICAL NM CONDITIONING
The circuit just described includes all the brain
structures required for the successful acquisition and
retention of the CR in the delay classical conditioning
paradigm. For example, in a well-trained animal, all
the neural tissue above the level of the midbrain can be
completely removed without affecting the retention
and expression of the CR. In other words, removing
the entire neocortex, thalamus, basal ganglia, and
limbic system, including the hippocampus, has no
effect on the CR.
For trace classical conditioning, these structures are
also essential; however, the hippocampus is also
required. If an interval of at least 500 msec separates
the offset of the CS and the onset of the US,
hippocampal lesions prevent CR acquisition and
retention.
XIV. THE AMYGDALA IS ESSENTIAL FOR
THE ACQUISITION AND RETENTION OF THE
CLASSICALLY CONDITIONED FEAR RESPONSE
Although amygdala lesions do not affect the acquisition or retention of eyeblink/NM classical conditioning, the amygdala is essential for the acquisition and
retention of the classical conditioned fear response.
For example, in rats, when a tone CS is paired with a
shock US several times, a conditioned fear response
develops. In other words, after pairing the CS will
cause a fear response of freezing. The rat that has been
conditioned will hold completely still when the CS is
presented. Amygdala lesions completely prevent rats
from learning or retaining this fear response. Thus,
classical condition has revealed that the amygdala is a
critical brain structure for emotional fear learning.
XV. BRAIN STRUCTURES INVOLVED IN HUMAN
CLASSICAL CONDITIONING
Although studies of classical conditioning in humans
began to wane in the 1960s, particularly for eyeblink
classical conditioning, within the past 10 years there
has been a resurgence of experimental work that can
largely be attributed to the success of classical
conditioning as a tool to study brain function in the
experimental animal. Currently, our understanding of
how different human brain structures contribute to
classical condition lags far behind what is known in the
animal and will likely never approach the level of
precision that is possible with animal studies. Nevertheless, there has recently been much progress with
relating classical conditioning to brain function in
humans.
Recent findings from human studies have been
remarkably consistent with previous work with animal
studies of conditioning. For example, work in rats has
convincingly demonstrated the importance of the
amygdala in fear classical conditioning. Studies using
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CLASSICAL CONDITIONING
brain imagining methods such as positron emission
tomography (PET) and functional magnetic resonance
image (fMRI) have shown that fear classical conditioning activates the amygdala. Additionally, humans
with bilateral degeneration of the amygdala, as a result
of Urbach–Wiethe disease, show an impaired ability to
acquire fear classical conditioning.
Results from human studies of eyeblink classical
conditioning have also been remarkably consistent
with those of studies in rabbits. For example, work
with rabbits clearly indicates that the cerebellum is
critical for acquisition of delay classical conditioning.
Humans with cerebellar damage are also severely
impaired on eyeblink classical conditioning. Humans
with bilateral hippocampal damage due to anoxia are
normal at acquiring CRs in the delay classical
conditioning paradigm, but they are impaired when
tested on trace classical conditioning. These results are
entirely consistent with the animal work. Imagining
studies using PET and fMRI have also consistently
identified the cerebellum and hippocampus as being
activated during classical conditioning of the eyeblink
response.
In addition to supporting previous work in animals,
human eyeblink conditioning studies have also extended our understanding of brain function in several
interesting ways. For example, it has been reported
that the knowledge that humans sometime acquire
about the stimulus contingencies of the conditioning
experiment (e.g., the CS predicts the US) is an
important variable for trace conditioning but irrelevant or superfluous for delay eyeblink conditioning.
Humans with hippocampal damage fail to acquire this
knowledge and accordingly fail to acquire trace
conditioning while being unaffected on delay conditioning.
It has repeatedly been reported that subjects with
Alzheimer’s disease and those with probable Alzheimer’s disease are impaired on delay classical conditioning of the eyeblink response. At first, this finding
did not appear to be congruent with the animal work
because Alzheimer’s disease does not affect the
cerebellum or other brain stem structures that are
critical for delay conditioning. However, work in
rabbits has shown that although the hippocampus can
BrainSoft.ir
be removed without
affecting acquisition in the delay
paradigm, disrupting the hippocampus by inactivating
the cholinergic input to the hippocampus can disrupt
delay conditioning. Alzheimer’s disease disrupts the
septohippocampal cholinergic system and it is this
disruption that likely causes the impairment in delay
eyeblink conditioning. If fact, this classical conditioning paradigm is so sensitive to the early effects of
Alzheimer’s disease that, it has been proposed as a
simple neuropsychological test for Alzheimer’s. Finally, humans with autism, a developmental disorder
characterized by severe impairments in communication and social relating and by ritualistic and repetitive
patterns of behavior, also show abnormalities in the
cerebellum. Subjects with autism also show abnormal
acquisition and extinction of the CR. This finding
further supports the involvement of the cerebellum in
classical eyeblink conditioning.
See Also the Following Articles
BEHAVIORAL NEUROGENETICS d COGNITIVE
PSYCHOLOGY, OVERVIEW d INTELLIGENCE d
REINFORCEMENT, REWARD, AND PUNISHMENT
Suggested Reading
Gormezano, I., Prokasy, W. F., and Thompson, R. F. (Eds.) (1987).
Classical Conditioning. Erlbaum, Hillsdale, NJ.
Green, J. T., and Woodruff-Pak, D. S. (2000). Eyeblink classical
conditioning: Hippocampal formation is for neutral stimulus
associations as cerebellum is for association-response. Psychol.
Bull. 126, 138–158.
Kim, J. J., and Thompson, R. F. (1997). Cerebellar circuits and
synaptic mechanisms involved in classical eyeblink conditioning.
Trends Neurosci. 20, 177–181.
Pavlov, I. P. (1927). Conditioned Reflexes (G. V. Anrep, Trans.).
Oxford Univ. Press, London.
Woodruff-Pak, D. S., and Steinmetz, J. E. (Eds.) (2000a). Eyeblink
Classical Conditioning: Volume IFApplications in Humans.
Kluwer, Boston.
Woodruff-Pak, D. S., and Steinmetz, J. E. (Eds.) (2000b). Eyeblink
Classical Conditioning: Volume IIFAnimal Models. Kluwer,
Boston.