CAMPBELL BIOLOGY IN FOCUS

Urry • Cain • Wasserman • Minorsky • Jackson • Reece

37
Neurons, Synapses,
and Signaling

Lecture Presentations by
Kathleen Fitzpatrick and Nicole Tunbridge

© 2014 Pearson Education, Inc.

Overview: Lines of Communication

 The cone snail kills prey with venom that disables

neurons
 Neurons are nerve cells that transfer information
within the body
 Neurons use two types of signals to communicate:
electrical signals (long distance) and chemical
signals (short distance)

© 2014 Pearson Education, Inc.

 Figure 37.1

© 2014 Pearson Education, Inc.

 Interpreting signals in the nervous system involves
sorting a complex set of paths and connections
 Processing of information takes place in simple
clusters of neurons called ganglia or a more
complex organization of neurons called a brain

© 2014 Pearson Education, Inc.

Concept 37.1: Neuron structure and organization
reflect function in information transfer
 The neuron is a cell type that exemplifies the close
fit of form and function that often arises over the
course of evolution

© 2014 Pearson Education, Inc.

Neuron Structure and Function

 Most of a neuron’s organelles are in the cell body

 Most neurons have dendrites, highly branched
extensions that receive signals from other neurons
 The single axon, a much longer extension, transmits
signals to other cells
 The cone-shaped base of an axon, where signals are
generated, is called the axon hillock

© 2014 Pearson Education, Inc.

Video: Dendrites
 Figure 37.2

Dendrites
Stimulus

Axon
Nucleus hillock

Cell
body
Presynaptic
cell Axon
Signal
direction
Synapse
Synaptic terminals
Synaptic
terminals

Postsynaptic cell
Neurotransmitter

© 2014 Pearson Education, Inc.

 The branched ends of axons transmit signals to
other cells at a junction called the synapse
 At most synapses, chemical messengers called
neurotransmitters pass information from the
transmitting neuron to the receiving cell

© 2014 Pearson Education, Inc.

 Neurons of vertebrates and most invertebrates
require supporting cells called glial cells
 In the mammalian brain, glia outnumber neurons
10- to 50-fold

© 2014 Pearson Education, Inc.

 Figure 37.3

80 m

Glia

Cell
bodies
of
neurons

© 2014 Pearson Education, Inc.

Introduction to Information Processing

 Nervous systems process information in three

stages
 Sensory input
 Integration
 Motor output

© 2014 Pearson Education, Inc.

 Figure 37.4

Sensory input

Integration
Sensor

Motor output

Processing center

Effector

© 2014 Pearson Education, Inc.

 Sensory neurons transmit information from eyes
and other sensors that detect external stimuli or
internal conditions
 This information is sent to the brain or ganglia, where
interneurons integrate the information
 Neurons that extend out of the processing centers
trigger muscle or gland activity
 For example, motor neurons transmit signals to
muscle cells, causing them to contract

© 2014 Pearson Education, Inc.

 In many animals, neurons that carry out integration
are organized in a central nervous system (CNS)
 The neurons that carry information into and out
of the CNS form the peripheral nervous system
(PNS)
 PNS neurons, bundled together, form nerves

© 2014 Pearson Education, Inc.

 Figure 37.5

Dendrites

Axon

Cell
body

Portion
of axon

Sensory neuron Interneurons Motor neuron

© 2014 Pearson Education, Inc.

Concept 37.2: Ion pumps and ion channels
establish the resting potential of a neuron
 The inside of a cell is negatively charged relative to
the outside
 This difference is a source of potential energy,
termed membrane potential
 The resting potential is the membrane potential of
a neuron not sending signals
 Changes in membrane potential act as signals,
transmitting and processing information

© 2014 Pearson Education, Inc.

Formation of the Resting Potential

 K and Na play an essential role in forming the

resting potential
 In most neurons, the concentration of K  is highest
inside the cell, while the concentration of Na  is
highest outside the cell
 Sodium-potassium pumps use the energy of ATP
to maintain these K and Na gradients across the
plasma membrane

© 2014 Pearson Education, Inc.

Animation: Resting Potential
Right click slide / Select play
 Table 37.1

© 2014 Pearson Education, Inc.

 Figure 37.6

Key
OUTSIDE
Na OF CELL
K

Sodium-
potassium
pump

Potassium
channel

Sodium INSIDE
channel OF CELL
© 2014 Pearson Education, Inc.
 The opening of ion channels in the plasma
membrane converts the chemical potential energy of
the ion gradients to electrical potential energy
 Ion channels are selectively permeable, allowing
only certain ions to pass through
 A resting neuron has many open potassium
channels, allowing K to flow out
 The resulting buildup of negative charge within the
neuron is the major source of membrane potential

© 2014 Pearson Education, Inc.

Modeling the Resting Potential

 Resting potential can be modeled by an artificial

membrane that separates two chambers
 The concentration of KCl is higher in the inner
chamber and lower in the outer chamber
 K diffuses down its gradient to the outer chamber
 Negative charge (Cl−) builds up in the inner chamber
 At equilibrium, both the electrical and chemical
gradients are balanced

© 2014 Pearson Education, Inc.

 Figure 37.7

Inner −90 mV Outer Inner 62 mV Outer

chamber chamber chamber chamber

140 mM 5 mM 15 mM 150 mM
KCI KCI NaCI NaCI

Cl−

K Na
Potassium Cl−
Sodium
channel
channel
Artificial
membrane

(a) Membrane selectively permeable (b) Membrane selectively permeable

to K to Na
5 mM 150 mM
EK  62 mV log 140 mM  −90 mV ENa  62 mV log 15 mM  62 mV

© 2014 Pearson Education, Inc.

 The equilibrium potential (Eion) is the membrane
voltage for a particular ion at equilibrium and can be
calculated using the Nernst equation

 The equilibrium potential for K is −90 mV

 The resting potential of an actual neuron is about −60
to −80 mV because a small amount of Na diffuses
into the cell

© 2014 Pearson Education, Inc.

 In a resting neuron, the currents of K  and Na are
equal and opposite, and the resting potential across
the membrane remains steady

© 2014 Pearson Education, Inc.

Concept 37.3: Action potentials are the signals
conducted by axons
 Researchers can record the changes in membrane
potential when a neuron responds to a stimulus
 Changes in membrane potential occur because
neurons contain gated ion channels that open or
close in response to stimuli

© 2014 Pearson Education, Inc.

 Figure 37.8

Technique

Microelectrode
Voltage
recorder

Reference
electrode

© 2014 Pearson Education, Inc.

 Figure 37.9

Ions
Change in
membrane
potential
(voltage)

Ion
channel

(a) Gate closed: No ions (b) Gate open: Ions flow

flow across membrane. through channel.

© 2014 Pearson Education, Inc.

Hyperpolarization and Depolarization

 When gated K channels open, K diffuses out,

making the inside of the cell more negative
 This is hyperpolarization, an increase in magnitude
of the membrane potential

© 2014 Pearson Education, Inc.

 Figure 37.10

Stimulus Stimulus Strong depolarizing stimulus

50 50 50
Action
potential
Membrane potential (mV)

Membrane potential (mV)

Membrane potential (mV)
0 0 0

Threshold Threshold Threshold

−50 −50 −50

Resting Resting Resting

potential potential potential
Hyperpolarizations Depolarizations
−100 −100 −100
0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5 6
Time (msec) Time (msec) Time (msec)

(a) Graded hyperpolarizations (b) Graded depolarizations (c) Action potential triggered by
produced by two stimuli produced by two stimuli a depolarization that reaches
that increase membrane that increase membrane the threshold
permeability to K permeability to Na

© 2014 Pearson Education, Inc.

 Figure 37.10a
(a) Graded hyperpolarizations
Stimulus
produced by two stimuli
that increase membrane 50
permeability to K

Membrane potential (mV)

0

Threshold
−50

Resting
potential
Hyperpolarizations
−100
0 1 2 3 4 5
Time (msec)
© 2014 Pearson Education, Inc.
 Opening other types of ion channels triggers a
depolarization, a reduction in the magnitude of the
membrane potential
 For example, depolarization occurs if gated Na 
channels open and Na diffuses into the cell

© 2014 Pearson Education, Inc.

 Figure 37.10b

(b) Graded depolarizations Stimulus

produced by two stimuli
that increase membrane 50
permeability to Na

Membrane potential (mV)

0

Threshold
−50

Resting
potential
Depolarizations
−100
0 1 2 3 4 5
Time (msec)
© 2014 Pearson Education, Inc.
Graded Potentials and Action Potentials

 Graded potentials are changes in polarization

where the magnitude of the change varies with the
strength of the stimulus
 Graded potentials decay with distance from the
source

© 2014 Pearson Education, Inc.

 If a depolarization shifts the membrane potential
sufficiently, it results in a massive change in
membrane voltage, called an action potential
 Action potentials have a constant magnitude and
transmit signals over long distances
 They arise because some ion channels are voltage
gated, opening or closing when the membrane
potential passes a certain level

© 2014 Pearson Education, Inc.

 Action potentials occur whenever a depolarization
increases the membrane potential to a particular
value, called the threshold
 Action potentials are all or none

© 2014 Pearson Education, Inc.

 Figure 37.10c

(c) Action potential Strong depolarizing stimulus

triggered by a
depolarization that 50
Action
reaches the threshold potential

Membrane potential (mV)

0

Threshold
−50

Resting
potential
−100
0 1 2 3 4 5
Time (msec)
© 2014 Pearson Education, Inc.
Generation of Action Potentials: A Closer Look

 An action potential can be considered as a series of

stages
 At resting potential
1. Most voltage-gated sodium (Na) channels are
closed; most of the voltage-gated potassium (K )
channels are also closed

© 2014 Pearson Education, Inc.

Animation: Action Potential
Right click slide / Select play
Video: How Neurons Work
 Figure 37.11
Key
Na
K

3 Rising phase of the action potential

4 Falling phase of the action potential

50
Action
potential

Membrane potential
3
0

(mV)
2 4

Threshold
−50
1 1
5

Resting potential
2 Depolarization −100
Time

OUTSIDE OF CELL Sodium Potassium

channel channel

5 Undershoot
INSIDE OF CELL
Inactivation loop

1 Resting state
© 2014 Pearson Education, Inc.
 Figure 37.11a

Key
Na
K
OUTSIDE OF CELL Sodium Potassium
channel channel

INSIDE OF CELL
Inactivation loop

1 Resting state

© 2014 Pearson Education, Inc.

 When stimulus depolarizes the membrane
2. Some gated Na+ channels open first and Na flows
into the cell
3. During the rising phase, the threshold is crossed,
and the membrane potential increases
4. During the falling phase, voltage-gated Na channels
become inactivated; voltage-gated K  channels
open, and K flows out of the cell

© 2014 Pearson Education, Inc.

 Figure 37.11b

Key
Na
K

2 Depolarization

© 2014 Pearson Education, Inc.

 Figure 37.11c

Key
Na
K

3 Rising phase of the action potential

© 2014 Pearson Education, Inc.

 Figure 37.11d

Key
Na
K

4 Falling phase of the action potential

© 2014 Pearson Education, Inc.

 5. During the undershoot, membrane permeability to
K is at first higher than at rest, and then voltage-
gated K channels close and resting potential is
restored

© 2014 Pearson Education, Inc.

 Figure 37.11e

Key
Na
K

5 Undershoot

© 2014 Pearson Education, Inc.

 Figure 37.11f

50
Action
Membrane potential potential

3
0
(mV)

2 4

Threshold
−50
1 1
5

Resting potential
−100
Time

© 2014 Pearson Education, Inc.

 During the refractory period after an action
potential, a second action potential cannot be
initiated
 The refractory period is a result of a temporary
inactivation of the Na channels
 For most neurons, the interval between the start of
an action potential and the end of the refractory
period is only 1–2 msec

© 2014 Pearson Education, Inc.

Conduction of Action Potentials

 At the site where the action potential is initiated

(usually the axon hillock), an electrical current
depolarizes the neighboring region of the axon
membrane
 Action potentials travel only toward the synaptic
terminals
 Inactivated Na channels behind the zone of
depolarization prevent the action potential from
traveling backward

© 2014 Pearson Education, Inc.

 Figure 37.12-1

Axon

Plasma
Action membrane
potential
1
Na Cytosol

© 2014 Pearson Education, Inc.

 Figure 37.12-2

Axon

Plasma
Action membrane
potential
1
Na Cytosol

Action
K potential
2
Na

K

© 2014 Pearson Education, Inc.

 Figure 37.12-3

Axon

Plasma
Action membrane
potential
1
Na Cytosol

Action
K potential
2
Na

K
Action
K
potential
3
Na

K
© 2014 Pearson Education, Inc.
Evolutionary Adaptations of Axon Structure

 The speed of an action potential increases with the

axon’s diameter
 In vertebrates, axons are insulated by a myelin
sheath, which enables fast conduction of action
potentials
 Myelin sheaths are produced by glia—
oligodendrocytes in the CNS and Schwann cells
in the PNS

© 2014 Pearson Education, Inc.

 Figure 37.13
Node of Ranvier
Layers of myelin
Axon

Schwann
cell
Schwann
cell
Axon Nodes of
Myelin Ranvier Nucleus of
sheath Schwann cell

0.1 m
© 2014 Pearson Education, Inc.
 Figure 37.13a

0.1 m

© 2014 Pearson Education, Inc.

 Action potentials are formed only at nodes of
Ranvier, gaps in the myelin sheath where voltage-
gated Na channels are found
 Action potentials in myelinated axons jump between
the nodes of Ranvier in a process called saltatory
conduction
 A selective advantage of myelination is space
efficiency

© 2014 Pearson Education, Inc.

 Figure 37.14

Schwann cell

Depolarized region
(node of Ranvier)

Cell body
Myelin
sheath
Axon

© 2014 Pearson Education, Inc.

Concept 37.4: Neurons communicate with other
cells at synapses
 At electrical synapses, the electrical current flows
from one neuron to another
 Most synapses are chemical synapses, in which a
chemical neurotransmitter carries information from
the presynaptic neuron to the postsynaptic cell

© 2014 Pearson Education, Inc.

 The presynaptic neuron synthesizes and packages
the neurotransmitter in synaptic vesicles located in
the synaptic terminal
 The arrival of the action potential causes the release
of the neurotransmitter
 The neurotransmitter diffuses across the synaptic
cleft and is received by the postsynaptic cell

© 2014 Pearson Education, Inc.

Animation: Synapse
Right click slide / Select play
Video: How Synapses Work
 Figure 37.15

Presynaptic cell Postsynaptic cell

Axon Synaptic vesicle

1 containing neurotransmitter
Synaptic
cleft
Postsynaptic
membrane
Presynaptic
membrane

3 4
K

Ca2 2

Voltage-gated Ligand-gated
Ca2 channel ion channels Na

© 2014 Pearson Education, Inc.

Generation of Postsynaptic Potentials

 Direct synaptic transmission involves binding of

neurotransmitters to ligand-gated ion channels
in the postsynaptic cell
 Neurotransmitter binding causes ion channels to
open, generating a postsynaptic potential

© 2014 Pearson Education, Inc.

 Postsynaptic potentials fall into two categories
 Excitatory postsynaptic potentials (EPSPs) are
depolarizations that bring the membrane potential
toward threshold
 Inhibitory postsynaptic potentials (IPSPs) are
hyperpolarizations that move the membrane potential
farther from threshold

© 2014 Pearson Education, Inc.

 The duration of postsynaptic potential is limited by
rapidly clearing neurotransmitter molecules from the
synaptic cleft
 Some neurotransmitters are recaptured into
presynaptic neurons to be repackaged into synaptic
vesicles
 Some are recaptured into glia to be used as fuel
or recycled to neurons
 Others are removed by simple diffusion or hydrolysis
of the neurotransmitter

© 2014 Pearson Education, Inc.

Summation of Postsynaptic Potentials

 The cell body of one postsynaptic neuron may

receive inputs from hundreds or thousands of
synaptic terminals
 A single EPSP is usually too small to trigger an
action potential in a postsynaptic neuron

© 2014 Pearson Education, Inc.

 Figure 37.16

Postsynaptic Synaptic
neuron terminals
of pre-
synaptic
neurons

5 m
© 2014 Pearson Education, Inc.
 Figure 37.17

Terminal branch
of presynaptic
neuron
E1 E1 E1 E1

E2 E2 E2 E2

Postsynaptic Axon
neuron hillock
I I I I
Membrane potential (mV)

Threshold of axon of
0
postsynaptic neuron Action Action
potential potential
Resting
potential

−70
E1 E1 E1 E1 E1  E2 E1 I E1  I

(a) Subthreshold, no (b) Temporal summation (c) Spatial summation (d) Spatial summation
summation of EPSP and IPSP

© 2014 Pearson Education, Inc.

 Figure 37.17a
Terminal branch
of presynaptic
neuron
E1 E1

E2 E2

Postsynaptic Axon
neuron hillock
I I
Membrane potential (mV)

Threshold of axon of
0
postsynaptic neuron Action
potential
Resting
potential

−70
E1 E1 E1 E1
(a) Subthreshold, no (b) Temporal summation
summation
© 2014 Pearson Education, Inc.
 If two EPSPs are produced in rapid succession, an
effect called temporal summation occurs

© 2014 Pearson Education, Inc.

 In spatial summation, EPSPs produced nearly
simultaneously by different synapses on the same
postsynaptic neuron add together
 The combination of EPSPs through spatial and
temporal summation can trigger an action potential

© 2014 Pearson Education, Inc.

 Figure 37.17b
Terminal branch
of presynaptic
neuron
E1 E1

E2 E2

Postsynaptic
neuron
I I
Membrane potential (mV)

0
Action
potential

−70
E1  E 2 E1 I E1  I
(c) Spatial summation (d) Spatial summation
of EPSP and IPSP
© 2014 Pearson Education, Inc.
 Through summation, an IPSP can counter the effect
of an EPSP
 The summed effect of EPSPs and IPSPs determines
whether an axon hillock will reach threshold and
generate an action potential

© 2014 Pearson Education, Inc.

Modulated Signaling at Synapses

 In some synapses, a neurotransmitter binds to a

receptor that is metabotropic
 In this case, movement of ions through a channel
depends on one or more metabolic steps

© 2014 Pearson Education, Inc.

 Binding of a neurotransmitter to a metabotropic
receptor activates a signal transduction pathway in
the postsynaptic cell involving a second messenger
 Compared to ligand-gated channels, the effects of
second-messenger systems have a slower onset but
last longer

© 2014 Pearson Education, Inc.

Neurotransmitters

 Signaling at a synapse brings about a response

that depends on both the neurotransmitter from
the presynaptic cell and the receptor on the
postsynaptic cell
 A single neurotransmitter may have more than a
dozen different receptors
 Acetylcholine is a common neurotransmitter in both
invertebrates and vertebrates

© 2014 Pearson Education, Inc.

Acetylcholine

 Acetylcholine is vital for functions involving muscle

stimulation, memory formation, and learning
 Vertebrates have two major classes of acetylcholine
receptor, one that is ligand gated and one that is
metabotropic

© 2014 Pearson Education, Inc.

 The best understood function of the ligand-gated ion
channel is in the vertebrate neuromuscular junction
 When acetylcholine released by motor neurons
binds to this receptor, the ion channel opens and an
EPSP is generated
 This receptor is also found elsewhere in the PNS
and in the CNS

© 2014 Pearson Education, Inc.

 A number of toxins disrupt neurotransmission by
acetylcholine
 These include the nerve gas sarin and a bacterial
toxin that causes botulism
 Acetylcholine is one of more than 100 known
neurotransmitters

© 2014 Pearson Education, Inc.

 Table 37.2

© 2014 Pearson Education, Inc.

 Table 37.2a

© 2014 Pearson Education, Inc.

 Table 37.2b

© 2014 Pearson Education, Inc.

 Table 37.2c

© 2014 Pearson Education, Inc.

Amino Acids

 Glutamate (rather than acetylcholine) is used at

the neuromuscular junction in invertebrates
 Gamma-aminobutyric acid (GABA) is the
neurotransmitter at most inhibitory synapses in the
brain
 Glycine also acts at inhibitory synapses in the CNS
that lies outside of the brain

© 2014 Pearson Education, Inc.

Biogenic Amines

 Biogenic amines include

 Norepinephrine and the chemically similar
ephinephrine
 Dopamine
 Serotonin
 They are active in the CNS and PNS
 Biogenic amines have a central role in a number of
nervous system disorders and treatments

© 2014 Pearson Education, Inc.

Neuropeptides

 Several neuropeptides, relatively short chains of

amino acids, also function as neurotransmitters
 Neuropeptides include substance P and
endorphins, which both affect our perception of
pain
 Opiates bind to the same receptors as endorphins
and produce the same physiological effects

© 2014 Pearson Education, Inc.

Gases

 Gases such as nitric oxide (NO) and carbon

monoxide (CO) are local regulators in the PNS
 Unlike most neurotransmitters, these are not stored
in vesicles but are instead synthesized as needed

© 2014 Pearson Education, Inc.

 Figure 37.UN01a

Radioactive
naloxone
1 Radioactive
naloxone and a
test drug are Drug
incubated with a
protein mixture.

2 Proteins are trapped on

a filter. Bound naloxone
is detected by measuring
radioactivity.

© 2014 Pearson Education, Inc.

 Figure 37.UN01b

© 2014 Pearson Education, Inc.

 Figure 37.UN02

Dendrites Axon
Cell body hillock Axon

Postsynaptic
cell
Presynaptic Signal Synapse
cell direction

© 2014 Pearson Education, Inc.

 Figure 37.UN03

Action potential

50
Membrane potential (mV)

Falling
phase
0 Rising
phase

Threshold (−55)
−50
Resting
potential
−70 Depolarization Undershoot
−100
0 1 2 3 4 5 6
Time (msec)

© 2014 Pearson Education, Inc.

 Figure 37.UN04

Electrode

Squid axon

© 2014 Pearson Education, Inc.