of dopamine and other neurotransmitters in

the brain. People with these disorders have

Cingulate cortex difficulty filtering out sensory stimuli. The
presence of excess dopamine may drive them
Frontal lobe to divert their attention to so many sensory
Fornix
stimuli that they have difficulty focusing on
the most important stimuli.
Thalamus

Learning and memory involve

Hippocampus long-term changes at synapses
Neurobiologists are beginning to understand
how the nervous system functions, including
Temporal lobe
how we learn and remember. Learning is the
process by which we acquire knowledge or
Amygdala skills as a result of experience. For learning to
occur, we must be able to remember what we
Olfactory bulbs
experience. Memory is the process of encod-
Hypothalamus ing, storing, and retrieving information or
learned skills.
An interesting question has been posed:
Figure 42-15 The limbic system To what extent are the brain’s functions
The limbic system consists of a ring of forebrain structures that surround the brain stem and are hard-wired, that is, preset? Many areas of the
interconnected by complex neural pathways. This system includes the amygdala, hippocampus, parts brain once thought to be hard-wired are now
of the prefrontal cortex, the cingulate cortex, and areas in the thalamus and hypothalamus. The limbic known to be flexible and capable of change.
system is important in assessing danger, in emotional expression, sexual behavior, motivation, and
learning.
Even animals with very simple nervous sys-
© Cengage Learning tems can learn to repeat behaviors associated
with reward and to avoid behaviors that cause
pain. Such changes in behavior are possible
Researchers first discovered in the 1950s that the limbic because of synaptic plasticity, the ability of synaptic connec-
system is part of an important motivational system when they tions to change in response to experience. Such change involves
implanted electrodes in certain areas of the brains of laboratory structure and function.
animals. They found that a rat quickly learns to press a lever that Familiar examples of plasticity in human motor skills
stimulates reward centers in the brain. In fact, the rat will press include learning to walk, ride a bicycle, or catch a baseball. At
the lever as many as 5000 times per hour, choosing this self- first, you were probably clumsy, but with practice your perfor-
stimulation over food and water, until it drops from exhaustion. mance became smoother and more precise. For that to happen,
The brain has reward centers that give us pleasure when changes must occur at synapses in neural circuits. Similarly, the
we carry out vital activities such as eating, drinking, and sex- ability to learn languages, solve problems, and perform scien-
ual activity. These centers are important in experiencing emo- tific experiments depends on synaptic plasticity.
tion and in motivation. When stimulated, they activate reward What are the mechanisms by which we learn diverse
circuits that allow us to feel pleasure in response to certain activities, such as skilled movement and the study of biology?
experiences. Canadian psychologist Donald O. Hebb proposed in 1949 that
The mesolimbic dopamine pathway, a major reward circuit, when two neurons connected by a synapse (i.e., presynaptic and
includes two important midbrain areas: the substantia nigra and postsynaptic neurons) are active simultaneously, the synapse
the adjacent ventral tegmental area. These areas, which extend is strengthened. We can credit Hebb for the axiom “Neurons
into behavioral control centers in the limbic system, contain the that fire together, wire together.” Hebb’s hypotheses have been
largest group of neurons in the brain that release dopamine. supported by experimental studies. Experience and practice do
Novel stimuli associated with reward or pleasure activate these affect how neural circuits in our brains organize themselves.
dopamine neurons. The neurons signal information about sur-
prising events or stimuli that predict rewards. Such signals may Learning involves the storage of information and its
motivate us to act when something important is happening. retrieval Implicit memory, also called procedural memory, is
Dopamine pathways are also important in the neurobiology of unconscious memory for perceptual and motor skills, such as
drug addiction (discussed later in this chapter). running, playing a guitar, or texting a message. Implicit mem-
As researchers continue to unravel the mechanisms of ory is about “how” to do something and involves repeating
dopamine pathways, we may better understand such disor- the behavior until it becomes routine. Declarative memory,
ders as attention deficit hyperactivity disorder (ADHD) and also called explicit memory, involves factual knowledge of
schizophrenia, conditions associated with excessive amounts people, places, or objects and requires conscious recall of the

Neural Regulation 891

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Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
 inquiring about
Have you been involved in a serious automo-
bile accident, or have you been the victim of a
violent crime? Are you a combat veteran of Iraq
or Afghanistan? Perhaps you are a survivor of
a natural disaster, such as a hurricane or earth-
quake. Or you may have endured childhood
neglect or abuse. If you are a survivor of any of
these experiences or of some other terrifying
event, you may have experienced the effects of
trauma. A traumatic experience is an event that
causes intense fear, helplessness, or horror and
that overwhelms normal coping and defense
mechanisms.
Most of us have strategies for effectively pro-
cessing moderately disturbing experiences. For
example, if you were involved in a minor car acci-
dent or were one of the millions of people who
watched on television as people were wounded
in war or pulled from the rubble of buildings
after earthquakes, you may have been disturbed
by the events you experienced or witnessed. You
probably processed what you saw and heard
by thinking about it and talking to your friends
and family about what happened. You may have
dreamed about your experience. As the brain
actively reviews and sorts out a disturbing expe-
rience, we try to make sense of what happened
and we process the memory. The emotional
intensity decreases, and we store the memory
along with other memories of more ordinary
past events. The memory of the uncomfortable
experience fades in importance and intensity.
Traumatic events are more difficult to pro-
cess than moderately disturbing events. If you
survived an experience in which you thought
you were going to die or be seriously hurt or if
you witnessed someone else being wounded
or killed, your body’s response to real or per-
ceived danger may be very intense. Years later,
your body may still be secreting abnormally
high amounts of stress hormones and you may
remain hyper-alert, your body poised to deal
with any new threat.
How does the brain respond in a traumatic
experience, and how does the experience affect
the brain? When danger threatens, the amyg-
dala sends messages to both the hypothalamus
(which signals the autonomic division of the ner-
vous system and the endocrine system) and the
cerebral cortex (which allows us to be aware of
our experience). The amygdala is programmed
to remember the smells, sounds, and sensa-
tions that are part of the experience. Until the
memories of the experience are fully processed,
similar smells, sounds, and sensations remind
us of the traumatic event and trigger the body to
information. The hippocampus, part of the limbic system, is
critical in forming and retrieving declarative memories.
How long do you remember? You are constantly bom-
barded with thousands of bits of sensory information. At this
very moment, your eyes are receiving information about the
892 CHAPTER 42
Copyright 2015 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
The Neurobiology of Traumatic Experience
prepare for danger. The traumatized individual traumatic experiences, activity in Broca’s area
may experience fear and anxiety. decreases. This deactivation appears to be the
Because they are so overwhelming, trau- physiological basis for the difficulty that trauma
matic memories are very difficult to process. survivors have describing their experience in
They cause us so much discomfort and anxiety words. Trauma survivors have described a state
that we tend to avoid them rather than inten- of “speechless terror” that they experience dur-
tionally focus on them and sort them out. As a ing flashbacks of traumatic experiences. With-
result, traumatic memories seem to stay “stuck” out words, it is difficult to process and resolve
in the limbic system. When triggered, the experi- a traumatic experience.
ence may be replayed with its original emotional Based on many studies, it is clear that trau-
intensity (a flashback). Some trauma survivors matic experiences can cause both structural
develop post-traumatic stress disorder (PTSD), and functional changes in the brain. The exag-
a condition in which they experience (1) intru- gerated responses of the amygdala to harmless
sive thoughts, images, sensory experiences, stimuli perceived as threatening are discon-
memories, and dreams; (2) an urge to avoid nected from the influence of the prefrontal
reminders of the traumatic event; and (3) physi- cortex that would normally modulate the lim-
ological hyperarousal, a condition in which the bic system. Responses generated by the limbic
body remains on high-alert status, scanning the system are rooted in emotion rather than in
environment for potential danger. rationality and judgment (see figure). PTSD can
Several studies have shown an association severely affect and limit one’s life. Fortunately,
between prolonged trauma (e.g., severe child- this disorder can be resolved with appropriate
hood neglect or abuse) and long-term changes treatment.
in the brain. These changes include EEG abnor-
malities; smaller size of certain regions of the
Reminder of traumatic experience
brain; compromised right brain development
(trigger)
(the right brain is specialized for processing
information related to emotion, social interac-
tion, and physiological states); differences in
neural circuits connecting cortical and subcorti- Low response by medial
cal areas (which can decrease the individual’s prefrontal cortex
sense of self and lead to poor connections with (which normally inhibits
other people); abnormal concentrations of cer- limbic system)
tain neurotransmitters, which affect mood and
the ability to inhibit inappropriate behavior;
inappropriate modulation of the limbic sys- Does not inhibit
tem, in which its responses are exaggerated; limbic system
and long-term changes in the sympathetic ner-
vous system and endocrine response to stress,
including a faster, more intense response to Limbic system
stress. (including Hypothalamus
Neuroimaging studies have demonstrated amygdala)
changes in brain function, including over-response over responds
by the amygdala and decreased response by the
medial prefrontal cortex (which normally inhib-
its the amygdala). When the amygdala over-
responds, the individual experiences anxiety, Distress, Physiological
distress, and physiological hyperarousal. These anxiety hyperarousal
physiological states can lead to intense emo-
tional responses that are rooted in the traumatic
experience.
Broca’s area, a region in the posterior part of Emotional responses rooted
the left frontal cortex, is also affected by trauma. in traumatic experience
Broca’s area is critically important in generat-
ing words and thus in expressing language Some limbic system responses to reminders of
(see Fig. 42-12). Researchers have shown that traumatic experiences.
when subjects are exposed to accounts of their © Cengage Learning
words on this page, the objects around you, and the intensity
of the light in the room. At the same time, you may be hear-
ing a variety of sounds, such as music, your friends talking in
the next room, or the hum of an air conditioner. Your olfactory
epithelium may sense cologne or the smell of coffee. Maybe you
are eating as you read. Sensory receptors in your hands may be improved by careful encoding, such as by forming strong asso-
receiving information regarding the weight and position of your ciations between items you want to remember. On the other
book or notebook computer. We may hold such sensory infor- hand, unimportant, unused memories are typically forgotten
mation in immediate memory for fractions of a second. Most over time. Forgetting can be useful when it clears the brain of
sensory stimuli are not important to remember any longer and unnecessary information.
are filtered out.
Short-term memory lasts only for seconds or for a few min- Neurobiological changes occur during learning Short-
utes. Typically, we can hold only about seven chunks of infor- term memory involves changes in the neurotransmitter recep-
mation (e.g., seven words or numbers) at a time in short-term tors of postsynaptic neurons. These changes strengthen synaptic
memory. Short-term memory lets us recall information for a few connections. The receptors are linked by second messengers
minutes. When we look up a phone number, for example, we (e.g., cyclic AMP) to ion channels in the plasma membrane.
usually remember it only long enough to call it. If we need the In some types of learning, changes take place in presynaptic
same number an hour later, most of us have to look it up again. terminals or postsynaptic neurons that permanently enhance
When we select information for long-term memory, we or inhibit the transmission of impulses. In some cases, specific
must process it. The brain rehearses the material and encodes neurons may become more sensitive than usual to a particular
it. We recognize patterns and meaningfully associate the stim- neurotransmitter. Neurons typically transmit action potentials
uli to past experience or knowledge. We practice recalling the in bursts, and the amount of a neurotransmitter released by each
information. The hippocampus temporarily holds new infor- action potential may increase or decrease.
mation and may integrate various aspects of an experience, Repeated electrical stimulation of neurons causes a func-
including odors, sounds, and other information. The hip- tional change at synapses. When a presynaptic neuron contin-
pocampus helps place our experiences in categories so that ues to transmit action potentials at a high rate for a minute
they can be stored along with similar memories. We integrate or longer, there is a long-lasting strengthening of the connec-
new information with other knowledge already stored in the tion between the presynaptic and postsynaptic neurons. This
brain. increased strength of the synaptic connection is known as
Memory consolidation allows memories to be transferred long-term potentiation (LTP). (Potentiation is the process of
to the cerebral cortex and stored for long periods. Consolida- “strengthening or making more potent.”)
tion involves expression of genes and protein synthesis, and it In contrast, low-frequency stimulation of neurons results
depends on new neural connections at synapses. Time (sev- in a long-lasting decrease in the strength of their synaptic con-
eral minutes, hours, or even longer) is required for the brain to nections. This decrease is called long-term depression (LTD),
consolidate a new memory. which is not related to the mood disorder. Information storage
If a person suffers a brain concussion, memory of what and forgetting depend on the strengthening and weakening of
happened immediately before the incident may be completely synaptic connections brought about by LTP and LTD.
lost. This condition is known as retrograde amnesia. When Induction of LTP and LTD requires activation of two types
the hippocampus is damaged, long-term memory may not of glutamate receptors: NMDA receptors and AMPA receptors.
be impaired, and the patient may be able to recall informa- (Each of these receptors is named for the compound that
tion stored in the past. However, new experiences (and the artificially activates it. NMDA is the acronym for N-methyl-
short-term memories of them) can no longer be converted to D-aspartate, and AMPA stands for α-amino-3-hydroxyl-5-
long-term memories. methyl-4-isoxazole-propionate.) NMDA and AMPA receptors
Where are memories stored? When large areas of the mam- are present on the plasma membranes of postsynaptic neurons.
malian cerebral cortex are destroyed, information is lost some- They control the passage of calcium ions into neurons. NMDA
what in proportion to the extent of lost tissue. No specific area receptors respond to the neurotransmitter glutamate by open-
can be labeled the “memory bank.” Rather, memories seem to ing Ca2+ channels. However, when the postsynaptic neuron is at
be stored within many areas of the brain. Visual memories, for its resting potential, NMDA ion channels are blocked by Mg2+.
example, may be stored in the visual centers of the occipital A model for the mechanism of LTP is illustrated in
lobes; similarly, auditory memories may be stored in the tem- FIGURE 42-16. A presynaptic neuron releases glutamate, which
poral lobes. Memories are integrated in many areas of the brain, binds with AMPA receptors. The postsynaptic neuron
including association areas of the cerebral cortex, amygdala, becomes depolarized. If depolarization of the postsynap-
hippocampus, thalamus, and hypothalamus. Wernicke’s area tic neuron is sufficiently strong, Mg2+ move away from the
in the temporal lobe has been identified as an important asso- NMDA receptors, unblocking them. Glutamate can then bind
ciation area for complex thought processes. Neurons within the with these receptors, opening Ca2+ channels and letting Ca2+
association areas form interconnected pathways that permit move into the cell. Calcium ions appear to be an important
complicated information transfer. trigger for LTP.
Retrieval of information stored in long-term memory is of Calcium ions act as second messengers that initiate long-
considerable interest, especially to students! The challenge is term changes ultimately responsible for LTP. For example,
to find information when you need it. When you seem to for- calcium ions activate a Ca2+-dependent second-messenger
get something, the problem may be that you have not searched pathway that results in the insertion of more AMPA receptors
effectively for the memory. Information retrieval can be in the postsynaptic membrane. This step is important because

Neural Regulation 893

Copyright 2015 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
 key point

When glutamate binds to NMDA receptors, Ca2+ enter the postsynaptic neuron and activate intracellular signaling systems, leading to
changes responsible for LTP.
Presynaptic Presynaptic Presynaptic
neuron neuron neuron
1
Stimulated
presynaptic
neuron Glutamate
releases
glutamate. 4
If postsynaptic
3 neuron is
Ion channels strongly
Glutamate depolarized, 6
open, allowing
Na+ to pass into 2+ Mg2+ move Ca2+ cause
AMPA Mg 2+ Mg more AMPA
postsynaptic away from
receptor NMDA receptors 7
neuron. Na+
depolarize receptors, to be Ca2+ stimulate
2 Na+ Ca2+ allowing inserted Ca2+ release of NO,
membrane.
Glutamate Postsynaptic glutamate into which diffuses
binds with neuron to bind with membrane. into presynaptic
AMPA NMDA neuron and
them.
receptors on receptor 5 stimulates
postsynaptic blocked release of more
Ca2+ channels open. Signaling
neuron. by Mg2+ glutamate.
pathway
Retrograde
NO signal
(a) Activation of AMPA receptors. Glutamate (b) Activation of NMDA receptors. (c) Long-term potentiation. Calcium
released by a presynaptic neuron binds with The combination of strong stimulation ions activate pathways, leading to
AMPA receptors on the postsynaptic neuron. and glutamate binding activates changes that are ultimately responsible
Note that NMDA receptors are blocked by Mg2+. NMDA receptors. Calcium channels for LTP.
open, allowing Ca2+ to enter the
postsynaptic neuron.

Figure 42-16 A proposed model for the mechanism of long-term potentiation (LTP) predict Imagine that Ca2+ channels did
© Cengage Learning not open (in step 5). How would this affect
synaptic connections and LTP?

additional AMPA receptors increase sensitivity to glutamate. synthesis. In this process, protein kinase phosphorylates a tran-
More EPSPs (excitatory postsynaptic potentials) are produced, scription factor known as cyclic AMP response element binding
which strengthens the synapse (i.e., helps maintain the LTP). protein (CREB), which then turns on the transcription process
Recall from Chapter 41 that an EPSP is a change in membrane of certain genes. CREB has been shown to be a signaling mol-
potential that brings the neuron closer to its threshold level. ecule in the memory pathway in many animals, including fruit
Calcium ions also activate a pathway that leads to release flies and mice. The molecules and processes involved in learn-
of a retrograde signal, a signal that moves backward, from the ing and memory have been highly conserved during evolution.
postsynaptic neuron to the presynaptic neuron. The soluble gas
nitric oxide (NO) has been identified as the retrograde signal. Experience affects development and learning Many
This signal enhances neurotransmitter release by the presynap- studies have demonstrated synaptic plasticity in rats, mice, and
tic neuron. Note that this positive feedback loop strengthens the other laboratory animals exposed to enriched environments.
connection between the two neurons. In contrast with rats housed in standard cages and provided
with the basic necessities, those exposed to enriched environ-
Long-term memory involves gene expression Gene ments are given toys and other stimulating objects as well as
expression and protein synthesis take place during the process the opportunity to socially interact with other rats. Animals
of establishing long-term memory. This process involves slower, reared in an enriched environment exhibit increased synaptic
but longer-lasting, changes in synaptic connections. Long-term contacts, and they process and remember information more
memory depends on activated receptors linked to G proteins quickly than animals lacking such advantages. Mice exposed to
(see Chapter 6). Cyclic AMP acts as a second messenger. enriched environments develop significantly greater numbers
A high level of cyclic AMP activates a protein kinase that of neurons in the hippocampus and learn mazes faster than
enters the nucleus, leading to gene activation and protein control animals.

894 CHAPTER 42

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Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
 Early environmental stimulation can also enhance the
development of motor areas in the brain. For example, the 42.5 THE PERIPHERAL
brains of rats encouraged to exercise become slightly heavier
than those of control animals. Characteristic changes occur
NERVOUS SYSTEM
within the cerebellum, including the development of larger
dendrites. learning objectives
Apparently, during early life certain critical or sensitive 10 Describe the organization of the peripheral nervous system
periods of nervous system development occur that are influ- and compare its somatic and autonomic divisions.
enced by environmental stimuli. For example, when the eyes of 11 Contrast the sympathetic and parasympathetic divisions of
young mice first open, neurons in the visual cortex develop large the autonomic system and give examples of the effects of
numbers of dendritic spines (structures on which synaptic con- these systems on specific organs.
tact takes place). If the animals are kept in the dark and deprived
of visual stimuli, fewer dendritic spines form. If the mice are The peripheral nervous system consists of the sensory recep-
exposed to light later in life, some new dendritic spines form, tors, the nerves that link these receptors with the central ner-
but never as many as develop in a mouse reared in a normal vous system, and the nerves that link the CNS with effectors
environment. (muscles and glands). The somatic division of the PNS helps
Studies linking the development of the human brain with the body respond to changes in the external environment. The
environmental experience have demonstrated that early stimu- nerves and receptors that maintain homeostasis despite internal
lation is important for the sensory, motor, intellectual, and social changes make up the autonomic division.
development of children. Such studies argue for the importance
of informed parenting as well as for early childhood education
programs, such as Head Start. Investigators have also shown that The somatic division helps the body
environmental stimulation is needed to maintain the status of adjust to the external environment
the cerebral cortex in later life.
The somatic division of the PNS includes the receptors that
react to changes in the external environment, the sensory neu-
rons that inform the CNS of those changes, and the motor neu-
Language involves comprehension rons that adjust the positions of the skeletal muscles that help
and expression maintain the body’s posture and balance. In mammals 12 pairs
Language is a form of communication in which we use of cranial nerves emerge from the brain. They transmit infor-
words to symbolize objects and convey ideas. In about 97% of mation to the brain from the sensory receptors for smell, sight,
humans, including most individuals who are left-handed, the hearing, and taste. For example, cranial nerve II, the optic nerve,
areas of the brain responsible for language are located in the transmits signals from the retina of the eye to the brain. The
left hemisphere (see Fig. 42-12). Wernicke’s area, located in cranial nerves transmit information to the brain from general
the temporal lobe, is an important center for language com- sensory receptors, especially in the head region.
prehension. This area helps us recognize and interpret both Cranial nerves bring orders from the CNS to the volun-
spoken and written words. Wernicke’s area also helps us for- tary muscles that control movements of the eyes, face, mouth,
mulate the choice and sequence of words and transfers infor- tongue, pharynx, and larynx. Cranial nerve VII, the facial nerve,
mation to Broca’s area. Located near motor areas in the left transmits signals to the muscles used in facial expression and to
frontal lobe, Broca’s area controls our ability to speak. This the salivary glands.
area is also important in language processing and speech In humans 31 pairs of spinal nerves emerge from the spi-
comprehension. nal cord. Named for the general region of the vertebral column
from which they originate, they comprise 8 pairs of cervical,
12 pairs of thoracic, 5 pairs of lumbar, 5 pairs of sacral, and
checkpoint 42.4 1 pair of coccygeal spinal nerves. The ventral branches of several
• How is the human CNS protected? What is the function of the spinal nerves form tangled networks called plexi (sing., plexus).
cerebrospinal fluid? Within a plexus, the fibers of a spinal nerve may separate and
then regroup with fibers that originated in other spinal nerves.
• What are two main functions of the vertebrate spinal cord?
Thus, nerves emerging from a plexus consist of neurons from
• visualize Draw a lateral view of the human brain, label the
several different spinal nerves.
major structures, including the lobes; write the functions of each
lobe.
• connect What role does the limbic system play in emotions? The autonomic division regulates
in traumatic experience?
the internal environment
• connect In what ways does your success on a biol-
ogy exam depend on synaptic plasticity? (Include the roles The autonomic division of the PNS helps maintain homeosta-
of LTP, gene expression, and NMDA receptors in your sis in the internal environment. For example, it regulates the
answer.) heart rate and helps maintain a constant body temperature.

Neural Regulation 895

Copyright 2015 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.