2

Structure and Function

of the Nervous System
2 Structure and Function of the Nervous System

• Cells of the Nervous System

• Electrical Transmission within a Neuron
• Organization of the Nervous System
Cells of the Nervous System
Embryonic stem cells that form the nervous
system become two primary cell types:
• Neurons transmit information in the form of
electrical signaling.
• Glial cells provide metabolic
support, protection,
and insulation for neurons.
Figure 2.1 Varied shapes of neurons

Sensory neurons convert

physical stimuli into electrical
signals.

Interneurons, in brain and

spinal cord, form interacting
neural circuits; responsible
for conscious sensations,
recognition, memory,
decision-making, cognition.

Motor neurons direct

biobehavioral responses
appropriate for the situation.
Figure 2.2 Principal parts of neurons

Neurons have three parts:

• Soma—cell body; contains nucleus
and other organelles.
• Dendrites—projections from the
soma that receive information.
• Axon—extension that conducts
electrical signals from the cell body
to the terminal buttons.
Cells of the Nervous System

Like other cells, neurons are enclosed

by a semipermeable membrane and
are filled with salty cytoplasm.
They are surrounded by salty fluid
(extracellular fluid), from which they
take O2, nutrients, and drugs, and
into which they secrete metabolic
waste products.
Cells of the Nervous System

Like other cells, neurons have mitochondria,

responsible for generating energy from glucose.
Neurons require large amounts of ATP;
mitochondria are abundant where energy needs
are greatest.
Rate of ATP synthesis reflects neuron activity; this
is used in techniques that allow visualization of
brain function.
Cells of the Nervous System
Dendrites and soma receive
information from other cells
across the gap between them,
the synapse.
Dendrites and soma have
thousands of receptors.
The effects on receiving cells may
be excitatory or inhibitory.
Cells of the Nervous System

Convergence: A neuron
receives and integrates a vast
amount of information from
many cells.
Divergence: The integrated
information can be transmitted
to a few or thousands of other
neurons.
Dendrites are covered with short dendritic
spines that increase surface area.
Dendrites and their spines are constantly
modified and can change shape rapidly in
response to changes in synaptic transmission.
Cells of the Nervous System

Prolonged synaptic activity can also change

the number, size, and shape of dendritic
spines.
These changes occur throughout life and
permit us to continue to learn new
associations.
Axons transmit electrical signals
from the axon hillock (at the
soma) to the terminals.
A neuron usually has one axon, but
it may branch to form axon
collaterals.
Terminal buttons have synaptic
vesicles containing
neurotransmitter chemicals.
Cells of the Nervous System
Most axons are wrapped with myelin
sheath, a fatty insulating coating
created by layers of glial cells.
Schwann cells myelinate peripheral
nerves that serve muscles, organs,
and glands.
Oligodendroglia myelinate nerves in
the brain and spinal cord.
Cells of the Nervous System
Nodes of Ranvier are breaks in the myelin sheath, the sites at
which action potentials are regenerated.

The myelin sheath increases speed of conduction along the axon;

the thicker the myelin, the faster the conduction.
Cells of the Nervous System

The soma (cell body) performs

most metabolic functions.
The nucleus contains pairs of
chromosomes (strands of DNA)
a gene is a section of
chromosome that codes for a
specific protein.
Cells of the Nervous System

Although every cell contains the

full complement of DNA, each
cell type makes different
proteins for specific functions.
Neurons make enzymes needed
to synthesize neurotransmitters
and carry out other nerve cell
functions.
Cells of the Nervous System

Experiences can affect gene expression.

Prolonged stress and chronic drug use can turn production
of particular proteins on or off by modifying transcription
factors—nuclear proteins that promote or obstruct the
formation of mRNAs.
Cells of the Nervous System

Transcription: Production of
complementary mRNA from
coding regions of DNA; takes
place in nucleus.

Translation: Building of protein

molecules by linking amino
acids specified by the mRNA
blueprint; takes place on
ribosomes in the cytoplasm.
Cells of the Nervous System

Epigenetics: Control of gene

expression by chromosome
modifications that do not affect
the DNA code.

Chromatin remodeling: Acetylation,

methylation, or phosphorylation of lysine DNA methylation:
residues of histone tails loosens the chromatin, Attachment of methyl
allowing transcription factors to bind to the groups to a gene reduces
DNA and activate translation. its expression (blocks
translation).
represses gene expression by physically
limiting the access of transcription
factors.
Figure 2.6 Epigenetic regulation of gene transcription (Part 1)

Chromatin is a complex of
spherical histone proteins
around which the DNA
wraps.
Cells of the Nervous System

● Epigenetic modification of gene expression

○ is central to cell differentiation in the
developing fetus.
○ can be passed on to offspring if they
occur in germ-line cells.
(transgenerational)
○ related to environmental factors.
■ stress/ drug use

■ parents’ lifelong environmental

exposure can influence their
offspring’s behavior, metabolism, or
disease status.
Cells of the Nervous System

Epigenetics may explain some phenomena, such as:

• why monozygotic twins with identical genes do not always
develop the same disorders;
• the persistence of the drug-taking behavior characteristic of
addiction;
• complex disorders such as depression or autism that seem to
run in families and yet have no classic genetic transmission;
and
• the link between early abuse or neglect and clinical
depression.
Cells of the Nervous System

The ultimate goal for neuropharmacology is

to develop drugs that can manipulate
epigenetic factors to treat psychiatric
disorders that have genetic components,
such as autism, schizophrenia, depression,
Alzheimer’s disease, and others.
Cells of the Nervous System
Axoplasmic transport: Proteins made in the soma must be transported
to the axon terminals.

The cytoskeleton is a network of microtubules and neurofilaments that

provide shape and structure to the cell.

Microtubules form a track along which packets of proteins travel by the

action of motor proteins.
Abnormalities of the cytoskeleton feature
in Alzheimer’s disease.

The microtubule system breaks down and

axons shrivel up, preventing
communication between neurons.
Cells of the Nervous System

Many cell membrane proteins are receptors—initial sites of

action of neurotransmitters, hormones, and drugs.

Other proteins associated with the membrane are enzymes that

catalyze biochemical reactions.

Other membrane proteins form ion channels and

transporters for charged molecules, such as
amino acids, glucose, and metabolic products.

Ions such as potassium (K+), sodium (Na+),

chloride (Cl–), and calcium (Ca2+), needed for
neuron function can move only through ion
channels.
Cells of the Nervous System
Ion channels are specific for one or a few ions. Gated channels are normally
closed; they open in response to specific stimuli:
• Ligand-gated channel—opens when a ligand binds to a receptor.
• Voltage-gated channel—opens when the electrical potential across the
membrane is altered.
Figure 2.8 Ion channels (Part 3)
Some ion channels are modified by second messengers, which
Modification of a cause intracellular phosphorylation (addition of a phosphate
channel by a group) and regulate the state of the channel.
second
messenger,
which produces
intracellular
phosphorylation
(addition of a
phosphate
group) and
regulates the
state of the
channel.
Cells of the Nervous System
Glial cells:
• Schwann cells—form myelin
sheaths in peripheral nervous
system (PNS), wrap only one
axon, release growth factors,
and promote regeneration of
damaged axons.
• Oligodendroglia—form
myelin sheaths in central
nervous system (CNS) and
wrap many axons.
Cells of the Nervous System
Astrocytes provide structural support
for neurons and help maintain ionic
balance in the extracellular
environment, and they take up
excess neurotransmitters.

Microglia remove dying cells by

phagocytosis at sites of nerve
damage and are responsible for
immune response.
Electrical Transmission within a Neuron
Resting membrane potential:
Difference in electrical charge
between inside and outside
of cell.

At rest, inside of cell is more

negative: –70 millivolts (mV);
it is polarized.

There are more negative ions

(and amino acids) inside the
cell and more positive ions
outside.
Most ion channels are gated, but some K+
channels are not; K+ can move freely.

K+ moves into the cell because it is attracted

to the negatively charged particles
(electrostatic pressure).

K+ moves back out of cell when its

concentration rises (concentration
gradient).

Equilibrium potential for

potassium—when the two forces are The Na+–K+ pump moves 3 Na+ to the outside for every 2 K+
balanced. The membrane potential is still moved to the inside, helping to keep the inside of the cell
negative. Ions are pumped against their concentration
more negative inside (–70 mV). gradients; requires energy.
Electrical Transmission within a Neuron
All cell membranes are polarized, but neurons can undergo rapid change in membrane
potential that is propagated down the length of the axon—called the action
potential.

Threshold membrane potential for firing is

–50 mV. Voltage-gated Na+ channels open, generating a rapid change in membrane
potential.
Electrical Transmission within a Neuron
Various stimuli can disturb the membrane and open ion channels.

Channels open momentarily, causing small, local changes in ion distribution and
potential differences called local potentials.

If Na+ channels open, Na+ enters cell and causes local depolarization.

If Cl– channels are stimulated to open, Cl– enters cell and results in hyperpolarization,
which is inhibitory.

If gated K+ channels open, K+ leaves the cell, which also results in hyperpolarization.
Electrical Transmission within a Neuron
Because neurotransmitters act on the postsynaptic membrane,
the effects are called:
• Excitatory postsynaptic potentials (EPSPs) or
• Inhibitory postsynaptic potentials (IPSPs).
Local potentials are graded—the
larger the stimulus, the greater the
magnitude of hyperpolarization or
depolarization;

They also show summation, or

integration—several small
depolarizations can add up to
larger changes in membrane
potential.
Electrical Transmission within a Neuron

When hyperpolarizations and depolarizations occur at the same

time, they cancel each other out.

Neuron receptor areas receive information from thousands of

synaptic connections at any given instant.

Integration of EPSPs and IPSPs occurs in the axon hillock.

Electrical Transmission within a Neuron
If summation of local
potentials reaches the
threshold, large
numbers of Na+
channels open and
Na+ rushes into the
cell very quickly.

Causes rapid change in

membrane potential
from –50 mV to +40
mV (rising phase of
action potential).
Electrical Transmission within a Neuron
Then Na+ channels close and
cannot be opened for a fixed
period—the absolute
refractory period.

Action potential lasts only 1

millisecond.

During rising phase, changing

membrane potential opens
voltage-gated K+ channels;
K+ moves out of the cell and
the membrane returns to
resting potential.
Electrical Transmission within a Neuron
The membrane overshoots
resting potential and is
hyperpolarized until
excess K+ diffuses away.

During this time it is more

difficult to generate an
action potential—the
relative refractory
period.
Electrical Transmission within a Neuron
Action potentials are “all
or none”—size is
unrelated to amount of
stimulation.

Action potential moves

along axon because
Na+ ions spread
passively to nearby
regions, which
changes the
membrane potential to
threshold, opening
more Na+ channels.
Electrical Transmission within a Neuron
In myelinated axons, regeneration of the action potential occurs only at nodes of
Ranvier.

The conduction seems to jump along the axon—saltatory conduction.

Less energy is needed because Na+–K+ pumps are only at the nodes.
Electrical Transmission within a Neuron
Some drugs alter action potential conductance by blocking the
voltage-gated Na+ channels (e.g., Novocaine). These drugs are used
for local anesthesia.

Some antiepileptic drugs bind to closed Na+ channels. Since it takes

time for the drug to unbind, it prolongs the refractory state of the
channel, slowing down the firing rate.

Saxitoxin in shellfish exposed to red tides blocks Na+ channels

throughout the nervous system because it is ingested. Conduction
failure results in death by suffocation.

Tetrodotoxin, found in Japanese pufferfish, also blocks Na+ channels.

Table 2.2 Characteristics of Local Potentials and Action Potentials
Organization of the Nervous System
To understand anatomical relationships of nervous system components,
biologists use terminology to describe locations in three dimensions.

It is based on the neuraxis, an imaginary line beginning at the base of the

spinal cord and ending at the front of the brain.
Box 2.3 The Cutting Edge: Finding Your Way in the Nervous System (Part 2)
Organization of the Nervous System
Central nervous system (CNS): Brain and
spinal cord.

Peripheral nervous system (PNS):

• Somatic system—controls voluntary
muscles.
• Autonomic system—controls organs
and glands:
▪ Sympathetic division
▪ Parasympathetic division
Organization of the Nervous System
Somatic nervous system:
Spinal and cranial nerves.

Spinal nerves carry both

sensory and motor
information (mixed nerves).
Autonomic nervous system (ANS)
• Regulates internal environment by
innervating smooth muscles of
intestines and bladder, cardiac
muscle, and glands, including adrenal
and salivary glands.
• Controls digestion, blood pressure,
body temperature, and other functions.
Figure 2.17 Spinal nerves of the peripheral nervous system
Sensory afferent nerves
carry information to the
spinal cord; soma are in
the dorsal root ganglia.

Motor efferent nerves

result in voluntary
movement; soma are in
ventral horn.
Organization of the Nervous System
Cranial nerves (12 pairs) serve mostly the head and
neck.

Not all are mixed nerves—some have only sensory

or motor function.

Several innervate glands and organs and thus are

part of the autonomic nervous system.
 Organization of the Nervous System
Autonomic NS branches into SNS
and paraSNS
Sympathetic division: Dominates
during times of stress, excitement,
and exertion; the “fight-or-flight”
system.

It increases heart rate and blood

pressure, stimulates secretion of
adrenaline, and increases blood
flow to skeletal muscles.
Parasympathetic division dominates when energy reserves can be conserved
and stored for later use.

It increases salivation, digestion, and storage of glucose and other nutrients,

slows heart rate and decreases respiration.
Organization of the Nervous System
Axons of efferent sympathetic nerves
synapse with cells in the sympathetic
ganglia near the spinal cord.

Preganglionic neurons release the

neurotransmitter acetylcholine.

Axons of postganglionic neurons extend long

distances to target tissues and release
norepinephrine.
Organization of the Nervous System
Soma of efferent parasympathetic
neurons are in the brain (cranial
nerves III, VII, IX, and X) or spinal
cord at the sacral region.

The axons extend long distances to

synapse on cells in parasympathetic
ganglia that are close to individual
target organs.

Parasympathetic postganglionic
neurons are quite short and release
acetylcholine.
Organization of the Nervous System
Many psychotherapeutic drugs alter
norepinephrine or acetylcholine in
the brain to relieve symptoms.

However, altering these

neurotransmitters in the peripheral
nerves can produce side effects,
such as elevated blood pressure,
dry mouth, and urinary problems.

Eg. scopolamine

Eg. pseudophedrine
Table 2.3 Characteristics of the Sympathetic and Parasympathetic Divisions of the ANS
Organization of the Nervous System

Meninges: Layers of tissue that cover and

protect the brain and spinal cord.
Dura mater: Outermost layer; toughest.
Arachnoid has a weblike sublayer (the
subarachnoid space) filled with
cerebrospinal fluid (CSF).
Pia mater: Thin layer on top of nerve tissue.
Organization of the Nervous System

CSF surrounds brain and spinal cord, fills

the cerebral ventricles and the central
channel in the spinal cord.
It protects the brain and aids exchange of
nutrients and waste products between
brain and blood.
CSF is formed in the choroid plexus;
capillaries here do not have tight junctions
Organization of the Nervous System

The CNS has six regions—evident in

developing embryos.
Understanding brain development is
important in understanding effects of drugs
or toxins at different stages.
The CNS begins as the neural tube, and
develops into forebrain, midbrain,
hindbrain, and spinal cord.
Figure 2.19 Divisions of the central nervous system (Part 1)
Organization of the Nervous System

The organization is hierarchical; each level

has overlapping functions—higher levels
partially replicate the functions of lower
ones but provide increased behavioral
complexity and refined control.
Within each CNS region are nuclei (clusters
of cell bodies) and their associated axons
(tracts).
Figure 2.19 Divisions of the central nervous system (Part 2)
Organization of the Nervous System

Neurotrophic factors: neuron growth factors

that influence growth, cell differentiation
and survival, and maintenance of synaptic
connections.
NGF (nerve growth factor) is secreted by
peripheral organs; guides the growth of
axons to establish synapses with the target
organ.
Organization of the Nervous System

BDNF (brain-derived neurotrophic factor) is

release from skeletal muscle; guides motor
neuron development and survival.
Schwann cells release growth factor when
their axon is damaged; leads to
regeneration of the axon.
Neurotrophic factors are potential
therapeutic agents for neurodegenerative
Organization of the Nervous System

Spinal cord: Gray matter contains neuron

cell bodies; white matter is myelinated
axons.
Where it enters the skull, it enlarges into the
brain stem—medulla, pons, and midbrain.
Many cranial nerves originate in the brain
stem.
Figure 2.20 Spinal cord
Organization of the Nervous System

Medulla (myelencephalon): regulates heart

rate, digestion, respiration, blood pressure,
coughing, vomiting.
Drug overdoses often cause depression of
the respiratory center.
Area postrema, the vomiting center, has a
reduced blood–brain barrier; initiates
vomiting in response to toxins.
Figure 2.21 Two views of the human brain (Part 1)
Figure 2.21 Two views of the human brain (Part 3)
Organization of the Nervous System

Metencephalon (pons and cerebellum):

• Reticular formation—extends from pons
to medulla and midbrain; collection of
nuclei that influence arousal, attention,
sleep, and muscle tone.
• Locus coeruleus—a nucleus with axons
extending to many areas of the forebrain;
source of neurons that use
Organization of the Nervous System

Dorsal and median raphe nuclei: Source

of neurons that use serotonin as the
neurotransmitter.
Axons go to all forebrain areas and function
in sleep regulation, aggression and
impulsiveness, neuroendocrine functions,
and emotion.
Serotonin has a generally inhibitory effect.
Organization of the Nervous System

Cerebellum: Sensorimotor center; connects

to pons by axon bundles called cerebellar
peduncles.
Receives visual, auditory, and
somatosensory input, and information
about body position and balance from the
vestibular system.
Coordinates sensory information with motor
Organization of the Nervous System

Mesencephalon (midbrain) has two

divisions:
• Tectum—contains parts of the visual and
auditory systems.
• Tegmentum—contains structures
important in psychopharmacology.
Organization of the Nervous System

Tegmentum includes:
• Periaqueductal gray (PAG)—important
for modulation of pain; rich in opioid
receptors; important site for morphine
binding.
• Substantia nigra—cluster of cell bodies
whose long axons innervate the striatum
in the basal ganglia.
Organization of the Nervous System

Cells in the nigrostriatal tract use dopamine

as the neurotransmitter; critical for the
initiation and modulation of movement.
Cell death in the substantia nigra is the
cause of Parkinson’s disease.
Figure 2.22 The basal ganglia
Organization of the Nervous System

Ventral tegmental area (VTA): Cells also

use dopamine; some axons extend into the
limbic system—the mesolimbic tract.
Cells in the mesocortical tract project to
areas in the cortex (also use dopamine).
Organization of the Nervous System

Diencephalon: thalamus and hypothalamus.

• Thalamus receives sensory and motor
information and passes it on to the cortex.
▪ Allows cortex to focus on selective
sensory signals, and diminishes
significance of others.
Organization of the Nervous System

• Hypothalamus receives information

about the internal environment and
coordinates with the limbic system to
maintain internal states (homeostasis).
▪ Regulates body temperature, salt−water
balance, hunger, thirst, energy
metabolism, reproductive behaviors, and
emotional responses.
Figure 2.23 Hypothalamus
Organization of the Nervous System

The hypothalamus controls both the

autonomic nervous system and the
endocrine system.
Some axons descend into the brainstem to
nuclei of parasympathetic cranial nerves;
others extend to the posterior pituitary.
Some nuclei secrete hormones that travel to
the anterior pituitary and regulate
Organization of the Nervous System

The paraventricular nucleus in the

hypothalamus regulates hormonal
response to stress.
HPA axis: Stress response depends on the
interaction of the hypothalamus, pituitary
gland, and adrenal gland.
Overuse of the stress response leads to
damaging changes to brain and body.
Box 2.4 Of Special Interest: Neuroendocrine Response to Stress
Organization of the Nervous System

Telencephalon: includes cerebral cortex,

limbic system, and basal ganglia.
• Limbic system integrates emotional
responses and regulates motivated
behavior and learning.
• Basal ganglia are involved in motor
control.
Figure 2.24 Limbic system
Organization of the Nervous System

Hippocampus: closely associated with

establishment of new long-term memories
and spatial memory.
Also involved in clinical depression and
antidepressant drug treatment.
Organization of the Nervous System

Amygdala: coordinates various components

of emotional responses through profuse
connections with other brain areas.
The amygdala and limbic system play a
prominent role in discussions of
antidepressants, alcohol, and antianxiety
drugs.
Organization of the Nervous System

Cerebral cortex
• Tissue is convoluted, with deep grooves
(fissures), smaller grooves (sulci), and
bulges (gyri).
• Convolutions increase the surface area.
• Cells are arranged in six layers,
appearing gray because of high
concentration of cell bodies.
Figure 2.25 Lateral view of the exterior cerebral cortex
Organization of the Nervous System

Corpus callosum: Neural pathway that

connects the two hemispheres.
Each hemisphere has four lobes: parietal,
occipital, temporal, and frontal.
Each lobe has a primary cortex that
provides conscious awareness of sensory
experience and initial processing.
Organization of the Nervous System

Secondary cortex: Adjacent to primary

cortex areas; responsible for analyzing
information from primary areas, providing
perception of the stimulus. Also, where
memories are stored.
Tertiary association areas lay down
more-complex memories that involve
multiple sensory systems.
Organization of the Nervous System

In the frontal lobe, the primary motor cortex

mediates voluntary muscle movements.
Secondary motor cortex: memories for
well-learned motor sequences are stored.
Prefrontal cortex: critical for making
decisions, planning actions, and evaluating
optional strategies. This area is impaired in
may psychiatric disorders.
Organization of the Nervous System

Many nerves beginning in the cortex are

crossed—areas of the right cortex receive
sensory information and control motor
movements on the left side of the body,
and vice-versa.
Visual information: Left half of visual field of
each eye goes to the right occipital lobe
and right half of visual field of each eye
Organization of the Nervous System

Rats are commonly used as research

models.
Brain structures have been highly conserved
during mammalian evolution, so the basic
brain plan is similar in rats and humans.
Figure 2.26 Comparison of human and rat brains
Organization of the Nervous System

Relative size of brain areas differ.

Rats have much larger olfactory bulbs than
humans—sense of smell is more important
for the nocturnal rat.
Rat cerebral cortex is smooth and has no
gyri or fissures. Human cortex areas for
receiving and processing information and
functions such as speech, etc., are highly
Figure 2.27 Lateral view of the left hemisphere of human and rat brains