1. Neurons, Synapses, and Signaling37
Neurons, Synapses, and Signaling

2. 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) 2

3. Figure 37.1
Figure 37.1 What makes this snail such a deadly predator? 3

4. 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 4

5. 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 5

6. 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
Video: Dendrites 6

7. Dendrites Stimulus Axon hillock Nucleus Cell body Presynaptic cell
Figure 37.2
Dendrites
Stimulus
Axon
hillock
Nucleus
Cell
body
Presynaptic
cell
Axon
Signal
direction
Synapse
Synaptic terminals
Figure 37.2 Neuron structure
Synaptic
terminals
Postsynaptic cell
Neurotransmitter 7

8. 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 8

9. In the mammalian brain, glia outnumber neurons 10- to 50-fold
Neurons of vertebrates and most invertebrates require supporting cells called glial cells
In the mammalian brain, glia outnumber neurons 10- to 50-fold 9

10. 80 m Glia Cell bodies of neurons Figure 37.3
Figure 37.3 Glia in the mammalian brain
Cell
bodies of
neurons 10

11. Introduction to Information Processing
Nervous systems process information in three stages
Sensory input
Integration
Motor output 11

12. Sensory input Integration Sensor Motor output Processing center
Figure 37.4
Sensory input
Integration
Sensor
Motor output
Figure 37.4 Summary of information processing
Processing center
Effector 12

13. 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 13

14. PNS neurons, bundled together, form nerves
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 14

15. Dendrites Axon Cell body Portion of axon Sensory neuron Interneurons
Figure 37.5
Dendrites
Axon
Cell
body
Figure 37.5 Structural diversity of neurons
Portion
of axon
Sensory neuron
Interneurons
Motor neuron 15

16. 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 16

17. 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
Animation: Resting Potential 17

18. Table 37.1
Table 37.1 Ion concentrations inside and outside of mammalian neurons 18

19. Key OUTSIDE Na OF CELL K Sodium- potassium pump Potassium channel
Figure 37.6
Key
OUTSIDE
OF CELL
Na K
Sodium-
potassium
pump
Figure 37.6 The basis of the membrane potential
Potassium
channel
Sodium
channel
INSIDE
OF CELL 19

20. 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 20

21. 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 21

22. 140 mM KCI 150 mM NaCI Inner chamber −90 mV Outer chamber Inner
Figure 37.7
Inner
chamber
−90 mV
Outer
chamber
Inner
chamber
62 mV
Outer
chamber
140 mM
KCI
5 mM
KCI
15 mM
NaCI
150 mM
NaCI
Cl− K
Na
Cl−
Potassium
channel
Sodium
channel
Artificial
membrane
Figure 37.7 Modeling a mammalian neuron
(a) Membrane selectively permeable
to K
(b) Membrane selectively permeable
to Na
5 mM
140 mM
150 mM
15 mM
EK  62 mV
log
 −90 mV
ENa  62 mV
log
 62 mV 22

23. The equilibrium potential for K is −90 mV
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 23

24. In a resting neuron, the currents of K and Na are equal and opposite, and the resting potential across the membrane remains steady 24

25. 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 25

26. Technique Microelectrode Voltage recorder Reference electrode
Figure 37.8
Technique
Microelectrode
Voltage
recorder
Figure 37.8 Research method: intracellular recording
Reference
electrode 26

27. Ions Change in membrane potential (voltage) Ion channel
Figure 37.9
Ions
Change in
membrane
potential
(voltage)
Ion
channel
Figure 37.9 Voltage-gated ion channel
(a) Gate closed: No ions
flow across membrane.
(b) Gate open: Ions flow
through channel. 27

28. 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 28

29. (a) Graded hyperpolarizations produced by two stimuli
Figure 37.10
Stimulus
Stimulus
Strong depolarizing stimulus
50
50
50
Action
potential
Membrane potential (mV)
Membrane potential (mV)
Membrane potential (mV)
Threshold
Threshold
Threshold
−50
−50
−50
Resting
potential
Resting
potential
Resting
potential
Hyperpolarizations
Depolarizations
−100
−100
−100
Figure Graded potentials and an action potential in a neuron 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 6
Time (msec)
Time (msec)
Time (msec)
(a) Graded hyperpolarizations
produced by two stimuli
that increase membrane
permeability to K
(b) Graded depolarizations
produced by two stimuli
that increase membrane
permeability to Na
(c) Action potential triggered by
a depolarization that reaches
the threshold 29

30. (a) Graded hyperpolarizations produced by two stimuli
Figure 37.10a
(a) Graded hyperpolarizations
produced by two stimuli
that increase membrane
permeability to K
Stimulus
50
Membrane potential (mV)
Threshold
−50
Figure 37.10a Graded potentials and an action potential in a neuron (part 1: hyperpolarizations)
Resting
potential
Hyperpolarizations
−100 1 2 3 4 5
Time (msec) 30

31. 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 31

32. (b) Graded depolarizations produced by two stimuli
Figure 37.10b
(b) Graded depolarizations
produced by two stimuli
that increase membrane
permeability to Na
Stimulus
50
Membrane potential (mV)
Threshold
−50
Figure 37.10b Graded potentials and an action potential in a neuron (part 2: depolarizations)
Resting
potential
Depolarizations
−100 1 2 3 4 5
Time (msec) 32

33. 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 33

34. 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 34

35. Action potentials are all or none
Action potentials occur whenever a depolarization increases the membrane potential to a particular value, called the threshold
Action potentials are all or none 35

36. Strong depolarizing stimulus
Figure 37.10c
(c) Action potential
triggered by a
depolarization that
reaches the threshold
Strong depolarizing stimulus
50
Action
potential
Membrane potential (mV)
Threshold
−50
Figure 37.10c Graded potentials and an action potential in a neuron (part 3: action potential)
Resting
potential
−100 1 2 3 4 5
Time (msec) 36

37. Generation of Action Potentials: A Closer Look
An action potential can be considered as a series of stages
At resting potential
Most voltage-gated sodium (Na) channels are closed; most of the voltage-gated potassium (K) channels are also closed
Animation: Action Potential
Animation: How Neurons Work 37

38. Rising phase of the action potential
Figure 37.11
Key
Na K 3
Rising phase of the action potential 4
Falling phase of the action potential
50
Action
potential 3
Membrane potential
(mV) 2 4
Threshold
−50 1 1 5
Resting potential 2
Depolarization
−100
Time
Figure The role of voltage-gated ion channels in the generation of an action potential
OUTSIDE OF CELL
Sodium
channel
Potassium
channel 5
Undershoot
INSIDE OF CELL
Inactivation loop 1
Resting state 38

39. Key Na K Resting state OUTSIDE OF CELL Sodium channel Potassium
Figure 37.11a
Key
Na K
OUTSIDE OF CELL
Sodium
channel
Potassium
channel
Figure 37.11a The role of voltage-gated ion channels in the generation of an action potential (part 1: resting state)
INSIDE OF CELL
Inactivation loop 1
Resting state 39

40. When stimulus depolarizes the membrane
Some gated Na+ channels open first and Na flows into the cell
During the rising phase, the threshold is crossed, and the membrane potential increases
During the falling phase, voltage-gated Na channels become inactivated; voltage-gated K channels open, and K flows out of the cell 40

41. Key Na K Depolarization 2 Figure 37.11b
Figure 37.11b The role of voltage-gated ion channels in the generation of an action potential (part 2: depolarization) 2
Depolarization 41

42. Rising phase of the action potential
Figure 37.11c
Key
Na K
Figure 37.11c The role of voltage-gated ion channels in the generation of an action potential (part 3: rising phase) 3
Rising phase of the action potential 42

43. Falling phase of the action potential
Figure 37.11d
Key
Na K
Figure 37.11d The role of voltage-gated ion channels in the generation of an action potential (part 4: falling phase) 4
Falling phase of the action potential 43

44. 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 44

45. Key Na K Undershoot 5 Figure 37.11e
Figure 37.11e The role of voltage-gated ion channels in the generation of an action potential (part 5: undershoot) 5
Undershoot 45

46. Membrane potential (mV)
Figure 37.11f
50
Action
potential 3
Membrane potential
(mV) 2 4
Threshold
−50 1 1
Figure 37.11f The role of voltage-gated ion channels in the generation of an action potential (part 6: graph) 5
Resting potential
−100
Time 46

47. 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 47

48. 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 48

49. Axon Plasma Action membrane potential Cytosol 1 1 Na Figure 37.12-1
Figure Conduction of an action potential (step 1) 49

50. Axon Plasma Action membrane potential Cytosol Action potential 1 2 1
Figure
Axon
Plasma
membrane
Action
potential 1 1
Na
Cytosol
Action
potential K 2
Na
Figure Conduction of an action potential (step 2) K 50

51. Axon Plasma Action membrane potential Cytosol Action potential Action
Figure
Axon
Plasma
membrane
Action
potential 1
Na
Cytosol
Action
potential K 2
Na
Figure Conduction of an action potential (step 3) K
Action
potential K 3
Na K 51

52. 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 52

53. Node of Ranvier Layers of myelin Axon Schwann cell Schwann cell
Figure 37.13
Node of Ranvier
Layers of myelin
Axon
Schwann
cell
Schwann
cell
Nodes of
Ranvier
Axon
Myelin
sheath
Nucleus of
Schwann cell
Figure Schwann cells and the myelin sheath
0.1 m 53

54. Figure 37.13a
Figure 37.13a Schwann cells and the myelin sheath (TEM)
0.1 m 54

55. A selective advantage of myelination is space efficiency
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 55

56. Schwann cell Depolarized region (node of Ranvier) Cell body Myelin
Figure 37.14
Schwann cell
Depolarized region
(node of Ranvier)
Cell body
Myelin
sheath
Axon
Figure Saltatory conduction 56

57. 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 57

58. 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
Animation: Synapse
Animation: How Synapses Work 58

59. K Ca2 Na Presynaptic cell Postsynaptic cell Axon Synaptic vesicle
Figure 37.15
Presynaptic cell
Postsynaptic cell
Axon
Synaptic vesicle
containing neurotransmitter 1
Synaptic
cleft
Postsynaptic
membrane
Presynaptic
membrane 3 4
Figure A chemical synapse K
Ca2 2
Ligand-gated
ion channels
Voltage-gated
Ca2 channel
Na 59

60. 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 60

61. 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 61

62. 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 62

63. 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 63

64. Postsynaptic neuron Synaptic terminals of pre- synaptic neurons 5 m
Figure 37.16
Postsynaptic
neuron
Synaptic
terminals
of pre-
synaptic
neurons
5 m
Figure Synaptic terminals on the cell body of a postsynaptic neuron 64

65. Figure 37.17
Terminal branch
of presynaptic
neuron E1 E1 E1 E1 E2 E2 E2 E2
Postsynaptic
neuron
Axon
hillock I I I I
Threshold of axon of
postsynaptic neuron
Action
potential
Action
potential
Membrane potential (mV)
Resting
potential
Figure Summation of postsynaptic potentials
−70 E1 E1 E1 E1
E1  E2 E1 I
E1  I
(a) Subthreshold, no
summation
(b) Temporal summation
(c) Spatial summation
(d) Spatial summation
of EPSP and IPSP 65

66. Membrane potential (mV)
Figure 37.17a
Terminal branch
of presynaptic
neuron E1 E1 E2 E2
Postsynaptic
neuron
Axon
hillock I I
Threshold of axon of
postsynaptic neuron
Action
potential
Membrane potential (mV)
Resting
potential
Figure 37.17a Summation of postsynaptic potentials (part 1: subthreshold and temporal summation)
−70 E1 E1 E1 E1
(a) Subthreshold, no
summation
(b) Temporal summation 66

67. If two EPSPs are produced in rapid succession, an effect called temporal summation occurs67

68. 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 68

69. Membrane potential (mV)
Figure 37.17b
Terminal branch
of presynaptic
neuron E1 E1 E2 E2
Postsynaptic
neuron I I
Action
potential
Membrane potential (mV)
Figure 37.17b Summation of postsynaptic potentials (part 2: spatial summation)
−70
E1  E2 E1 I
E1  I
(c) Spatial summation
(d) Spatial summation
of EPSP and IPSP 69

70. 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 70

71. 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 71

72. 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 72

73. 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 73

74. 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 74

75. This receptor is also found elsewhere in the PNS and in the CNS
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 75

76. 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 76

77. Table 37.2
Table 37.2 Major neurotransmitters 77

78. Table 37.2a
Table 37.2a Major neurotransmitters (part 1: acetylcholine and amino acids) 78

79. Table 37.2b
Table 37.2b Major neurotransmitters (part 2: biogenic amines) 79

80. Table 37.2c
Table 37.2c Major neurotransmitters (part 3: neuropeptides and gases) 80

81. 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 81

82. 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 82

83. 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 83

84. 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 84

85. Proteins are trapped on a filter. Bound naloxone
Figure 37.UN01a
Radioactive
naloxone 1
Radioactive
naloxone and a
test drug are
incubated with a
protein mixture.
Drug
Figure 37.UN01 Skills exercise: interpreting data values expressed in scientific notation (part 1) 2
Proteins are trapped on
a filter. Bound naloxone
is detected by measuring
radioactivity. 85

86. Figure 37.UN01b
Figure 37.UN01 Skills exercise: interpreting data values expressed in scientific notation (part 2) 86

87. Dendrites Axon hillock Axon Cell body Postsynaptic cell Presynaptic
Figure 37.UN02
Dendrites
Axon
hillock
Axon
Cell body
Postsynaptic
cell
Presynaptic
cell
Signal
direction
Synapse
Figure 37.UN02 Summary of key concepts: neuron structure 87

88. Membrane potential (mV)
Figure 37.UN03
Action potential
50
Falling
phase
Rising
phase
Membrane potential (mV)
Threshold (−55)
−50
Resting
potential
Figure 37.UN03 Summary of key concepts: action potential
−70
Depolarization
Undershoot
−100 1 2 3 4 5 6
Time (msec) 88

89. Electrode Squid axon Figure 37.UN04
Figure 37.UN04 Test your understanding, question 9 (depolarizing stimulus) 89