1. Nervous System & Synapses

2. I. Neurons and Supporting Cells

3. Introduction to the Nervous System
Divided into:
Central nervous system: brain and spinal cord
Peripheral nervous system: cranial and spinal nerves
Tissue is composed of two types of cells:
Neurons that conduct impulses but generally can not divide.
Glial cells (neuroglia) that support the neurons and can not conduct impulses, but can divide

4. Neurons Structural and functional units of the nervous system
General functions
Respond to chemical and physical stimuli
Conduct electrochemical impulses
Release chemical regulators
Enable perception of sensory stimuli, learning, memory, and control of muscles and glands
Most can not divide, but can repair

5. General Structure of Neurons
Neurons vary in size and shape, but they all have:
A cell body that contains the nucleus, Nissl bodies, and other organelles; cluster in groups called nuclei in the CNS and ganglia in the PNS
Dendrites: receive impulses and conducts a graded impulse toward the cell body
Axon: conducts action potentials away from the cell body

6. Structure of Two Kinds of Neurons
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Dendrites
Axon hillock
Direction of
conduction
Collateral axon
(a)
Cell body
Axon
Axon
Direction of
conduction
(b)
Dendrites

7. Axons Vary in length from a few millimeters to a meter
Connected to the cell body by the axon hillock where action potentials are generated at the initial segment of the axon.
Can form many branches called axon collaterals
Covered in myelin with open spots called nodes of Ranvier

8. Axonal Transport
An active process needed to move organelles and proteins from the cell body to axon terminals
Fast component moves membranous vesicles
Slow components move microfilaments, microtubules, and proteins
Anterograde transport – from cell body to dendrites and axon; uses kinesin molecular motors
Retrograde transport – from dendrites and axon to the cell body; uses dynein molecular motors

9. Parts of a neuron Cell body Nucleus Dendrite Node of Ranvier Schwann
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Cell body
Nucleus
Dendrite
Node of
Ranvier
Schwann
cell nucleus
Myelinated
region
Axon
Axon hillock
Initial segment
of axon
Myelin

10. Classification of Neurons and Nerves
Functional classification of neurons – based on direction impulses are conducted
Sensory neurons: conduct impulses from sensory receptors to the CNS
Motor neurons: conduct impulses from the CNS to target organs (muscles or glands)
Association/interneurons: located completely within the CNS and integrate functions of the nervous system

11. Motor Neurons
Somatic motor neurons: responsible for reflexes and voluntary control of skeletal muscles
Autonomic motor neurons: innervate involuntary targets such as smooth muscle, cardiac muscle, and glands
Sympathetic – emergency situations; “fight or flight”
Parasympathetic – normal functions; “rest and digest”

12. Classification of Nerves
Nerves are bundles of axons located outside the CNS
Most are composed of both sensory and motor neurons and are called mixed nerves.
Some of the cranial nerves have sensory fibers only.
A bundle of axons in the CNS is called a tract.

13. Neuroglia Cells that are non-conducting but support neurons
Two types are found in the PNS:
Schwann cells (neurolemmocytes): form myelin sheaths around peripheral axons
Satellite cells (ganglionic gliocytes): support cell bodies within the ganglia of the PNS

14. Neuroglia, cont Four types are found in the CNS:
Oligodendrocytes: form myelin sheaths around the axons of CNS neurons
Microglia: migrate around CNS tissue and phagocytize foreign and degenerated material
Astrocytes: regulate the external environment of the neurons
Ependymal cells: line the ventricles and secrete cerebrospinal fluid

15. Types of CNS Neuroglial Cells
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Capillary
Neurons
Astrocyte
Oligodendrocyte
Perivascular
feet
Axons
Myelin sheath
Ependymal
cells
Cerebrospinal
fluid
Microglia

16. Neuroglial Cells & their Functions

17. Neurilemma and Myeline
Myelin sheath in the PNS
All axons in the PNS are surrounded by a sheath of Schwann cells called the neurilemma, or sheath of Schwann.
These cells wrap around the axon to form the myelin sheath in the PNS.
Gaps between Schwann cells, called nodes of Ranvier, are left open.

18. Neurilemma and Myelin Schwann cell Axon Myelin sheath Nucleus
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Schwann
cell
Axon
Myelin
sheath
Nucleus
Sheath of Schwann
(neurilemma)

19. Myelin Sheath in CNS
In the CNS, the myelin sheath is produced by oligodendrocytes.
One oligodendrocyte sends extensions to several axons and each wraps around a section of an axon
Produces the myelin sheath but not a neurilemma
Myelin gives these tissues (axons) a white color = white matter.
Gray matter is cell bodies and dendrites which lack myelin sheaths

20. Myelin Sheath in CNS Oligodendrocyte Node of Ranvier Myelin sheath
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Oligodendrocyte
Node of Ranvier
Myelin
sheath
Axon

21. Regeneration of a cut neuron
When an axon in the PNS is cut, the severed part degenerates, and a regeneration tube is formed by Schwann cells.
Growth factors are leased that stimulate growth of axon sprouts within the tube
New axon eventually connects to the undamaged axon or the effector

22. Regeneration of a Cut Neuron, cont
CNS axons are not as able to regenerate.
Death receptors form that promote apoptosis of oligodendrocytes
Inhibitory proteins in the myelin sheath prevents regeneration
Glial scars from astrocytes form that also prevent regeneration

23. Process of PNS Regeneration
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Motor neuron
cell body
Schwann
cells
Site of injury
Skeletal
muscle
fiber
(a)
Distal portion of nerve
fiber degenerates and
is phagocytosed
(b)
Proximal end of injured
nerve fiber regenerating
into tube of Schwann cells
(c)
Growth
(d)
Former connection
reestablished
(e)

24. Blood-Brain-Barrier
Capillaries in the brain do not have pores between adjacent cells but are joined by tight junctions.
Substances can only be moved by very selective processes of diffusion through endothelial cells, active transport, and bulk transport
Movement is transcellular not paracellular
Astrocytes influence the production of ion channels and enzymes that can destroy toxic substances by secreting glial-derived neurotrophic factor.
Creates problems with chemotherapy of brain diseases because many drugs can not penetrate the blood-brain barrier.

25. II. Electrical Activity in Axons

26. Resting Membrane Potential
Neurons have a resting potential of −70mV.
Established by large negative molecules inside the cell
Na+/K+ pumps
Permeability of the membrane to positively charged, inorganic ions
At rest, there is a high concentration of K+ inside the cell and Na+ outside the cell.

27. Altering Membrane Potential
Neurons and muscle cells can change their membrane potentials.
Called excitability or irritability
Caused by changes in the permeability to certain ions
Ions will follow their electrochemical gradient = combination of concentration gradient and attraction to opposite charges.
Flow of ions are called ion currents which occur in limited areas where ion channels are located

28. Changes in Membrane Potential
At rest, a neuron is considered polarized when the inside is more negative than the outside.
When the membrane potential inside the cell increases (becomes more positive), this is called depolarization.
A return to resting potential is called repolarization.
When the membrane potential inside the cell decreases (becomes more negative), this is called hyperpolarization.

29. Changes in Membrane Potential, cont
Depolarization occurs when positive ions enter the cell (usually Na+).
Hyperpolarization occurs when positive ions leave the cell (usually K+) or negative ions (Cl−) enter the cell.
Depolarization of the cell is excitatory.
Hyperpolarization is inhibitory.

30. Ion Gating
Changes in membrane potential are controlled by changes in the flow of ions through channels.
K+ has two types of channels:
Not gated (always open); sometimes called K+ leakage channels
Voltage-gated K+ channels; open when a particular membrane potential is reached; closed at resting potential
Na+ has only voltage-gated channels that are closed at rest; the membrane is less permeable to Na+ at rest.

31. Voltage Gated Na+ Channels
These channels open if the membrane potential depolarizes to −55mV.
This is called the threshold.
Sodium rushes in due to the electrochemical gradient.
Membrane potential climbs toward sodium equilibrium potential.
These channels are deactivated at +30mV.

32. A Voltage-Gated Ion Channel
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Channel closed
at resting membrane
potential
Channel open
by depolarization
(action potential)
Channel inactivated
during refractory
period

33. Voltage Gated K+ Channels
At around +30mV, voltage-gated K+ channels open, and K+ rushes out of the cell following the electrochemical gradient.
This makes the cell repolarize back toward the potassium equilibrium potential.

34. Action Potentials
At threshold membrane potential (−55mV), voltage-gated Na+ channels open, and Na+ rushes in. As the cell depolarizes, more Na+ channels are open, and the cell becomes more and more permeable to Na+.
This is a positive feedback loop.
Causes an overshoot of the membrane potential
Membrane potential reaches +30mV.
This is called depolarization

35. Action Potentials, cont
At +30mV, Na+ channels close, and K+ channels open.
Results in repolarization of membrane potential
This is a negative feedback loop

36. Action Potentials Sodium equilibrium potential +30 Caused by Na+
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Sodium
equilibrium
potential
+30
Caused by Na+
diffusion into axon
Membrane potential (millivolts)
Caused by K+
diffusion out of axon
–50
Resting membrane potential
–70
Potassium
equilibrium
potential 1 2 3 4
Time (milliseconds)
1. Gated Na+ channels open
2a. Inactivation of Na+
channels begins
2b. Gated K+ channels open
Na+ and K+ diffusion
3. Inactivation of
K+ channels begins
4. Gated Na+ and K+
channels closed 1 2 3 4
Time (milliseconds)

37. After-Hyperpolarization
Repolarization actually overshoots resting potential and gets down to −85mV.
This does not reach potassium equilibrium potential because voltage-gated K+ channels are inactivated as the membrane potential falls.
Na+/K+ pumps quickly reestablish resting potential.

38. All-or-None Law
Once threshold has been reached, an action potential will happen.
The size of the stimulus will not affect the size of the action potential; it will always reach +30mV.
The size of the stimulus will not affect action potential duration.

39. (all have same amplitude)
All-or-None Law
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Action potentials
(all have same amplitude)
–70 mV
RMP
Weakest
Strongest
Stimuli
(single, quick shocks)

40. Coding for Stimulus Intensity
A stronger stimulus will make action potentials occur more frequently. (frequency modulated)
A stronger stimulus may also activate more neurons in a nerve. This is called recruitment.

41. (sustained for indicated times)
Coding for Stimulus Intensity
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Action potentials
–70 mV
RMP On
Off On
Off
Strength On
Off
Stimulus
Stimulus
Stimulus
Time
Stimuli
(sustained for indicated times)

42. Refractory Periods
Action potentials can only increase in frequency to a certain point. There is a refractory period after an action potential when the neuron cannot become excited again.
The absolute refractory period occurs during the action potential. Na+ channels are inactive (not just closed).
The relative refractory period is when K+ channels are still open. Only a very strong stimulus can overcome this.
Each action potential remains a separate, all-or-none event.

43. Refractory Periods Absolute refractory period Relative refractory
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Absolute
refractory
period
Relative
refractory
period
(due to
inactivated
Na+ channels)
(due to continued
outward diffusion
of K+)
+30
Membrane potential (millivolts)
–55
–70 1 2 3 4 5
Time (milliseconds)

44. Cable Properties of Neurons
The ability of neurons to conduct charges through their cytoplasm
Poor due to high internal resistance to the spread of charges and leaking of charges through the membrane
Neurons could not depend on cable properties to move an impulse down the length of an axon.

45. Conduction of Nerve Impulses
When an action potential occurs at a given point on a neuron membrane, voltage- gated Na+ channels open as a wave down the length of the axon.
The action potential at one location serves as the depolarization stimulus for the next region of the axon

46. Conduction of Nerve Impulses
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Axon
Action
potential begins – – + + + + + + – – – – 1
Na+
Axon + + – – – – – – + + + +
Action potential
is regenerated here K+ + + – – + + – – + + – – 2
Na+ – – + + – – + + – – + + K+
Action potential
is regenerated here K+ + + + + – – – – – – + + 3
Na+ – – – – + + + + + + – – K+ =
Resting potential =
Depolarization =
Repolarization

47. Conduction in an unmyelinated axons
Axon potentials are produced down the entire length of the axon at every patch of membrane.
The conduction rate is slow because so many action potentials are generated, each one, an individual event.
The amplitude of each action potential is the same – conducted without decrement

48. Conduction in a myelinated neuron
Myelin provides insulation, improving the speed of cable properties.
Nodes of Ranvier allow Na+ and K+ to cross the membrane every 1−2 mm.
Na+ ion channels are concentrated at the nodes
Action potentials “leap” from node to node.
This is called saltatory conduction.

49. Conduction in a Myelinated Neuron
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Action potential
was here
Action potential
was here
Na+
Myelin + – – + + – + + – – – + + – – + + + – –
Axon
Na+
= Resting potential
= Depolarization
= Repolarization

50. Action Potential Conduction Speed
Increased by:
Increased diameter of the neuron. This reduces resistance to the spread of charges via cable properties.
Myelination because of saltatory conduction
Examples
Thin, unmyelinated neuron speed 1.0m/sec
Thick, myelinated neuron speed 100m/sec

51. III. The Synapse

52. Introduction
A synapse is the functional connection between a neuron and the cell it is signaling
In the CNS, this second cell will be another neuron.
In the PNS, the second cell will be in a muscle or gland; often called myoneural or neuromuscular junctions

53. Introduction, cont’d
If one neuron is signaling another neuron, the first is called the presynaptic neuron, and the second is called the postsynaptic neuron.
A presynaptic neuron can signal the dendrite, cell body, or axon of a second neuron.
There are axodendritic, axosomatic, and axoaxonic synapses.
Most synapses are axodendritic and are 1 direction
Synapses can be electrical or chemical

54. Electrical Synapses
Electrical synapses occur in smooth muscle and cardiac muscle, between some neurons of the brain, and between glial cells.
Cells are joined by gap junctions.
Stimulation causes phosphorylation or dephosphorylation of connexin proteins to open or close the channels

55. Structure of Gap Junctions
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Cytoplasm
Plasma
membrane
of one cell
Plasma
membrane
of adjacent
cell
Two cells,
interconnected
by gap
junctions
Connexin
proteins
forming gap
junctions
Cytoplasm

56. Chemical Synapses
Most synapses involve the release of a chemical called a neurotransmitter from the axon’s terminal boutons.
The synaptic cleft is very small, and the presynaptic and postsynaptic cells are held close together by cell adhesion molecules (CAMs).

57. © John Heuser, Washington University School of Medicine, St. Louis, MO
Chemical Synapses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Mitochondria
Terminal
bouton of
axon
Synaptic
vesicles
Synaptic
cleft
Postsynaptic
cell (skeletal
muscle)
© John Heuser, Washington University School of Medicine, St. Louis, MO

58. Release of Neurotransmitter
Neurotransmitter is enclosed in synaptic vesicles in the axon terminal.
When the action potential reaches the end of the axon, voltage-gated Ca2+ channels open.
Ca2+ stimulates the fusing of synaptic vesicles to the plasma membrane and exocytosis of neurotransmitter.
A greater frequency of action potential results in more stimulation of the postsynaptic neuron.

59. Release of Neurotransmitter
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Axon
terminal
1. Action potentials
reach axon terminals
Action
potentials
Ca2+
Action
potentials
2. Voltage-gated Ca2+
channels open
Sensor protein +
Ca2+
Ca2+
Ca2+
Synaptic
vesicles
Ca2+– protein complex
3. Ca2+ binds to sensor
protein in cytoplasm
SNARE
complex
Docking
Ca2+
Ca2+
Fusion
Synaptic
cleft
Exocytosis
4. Ca2+-protein complex
stimulates fusion and
exocytosis of
neurotransmitter
Neurotransmitter
released
Postsynaptic cell
Ca2+

60. Actions of a Neurotransmitter
Neurotransmitter diffuses across the synapse, where it binds to a specific receptor protein.
The neurotransmitter is referred to as the ligand.
This results in the opening of chemically regulated ion channels (also called ligand-gated ion channels).

61. Graded Potential
When ligand-gated ion channels open, the membrane potential changes depending on which ion channel is open.
Opening Na+ or Ca2+ channels results in a graded depolarization called an excitatory postsynaptic potential (EPSP).
Opening K+ or Cl− channels results in a graded hyperpolarization called inhibitory postsynaptic potential (IPSP).

62. EPSPs vs IPSPs
EPSPs move the membrane potential closer to threshold; may require EPSPs from several neurons to actually produce an action potential
IPSPs move the membrane potential farther from threshold.
Can counter EPSPs from other neurons so summation of EPSPs and IPSPs at the initial segment of the axon (next to the axon hillock) determines whether an action potential occurs.

63. Some Cool Neurotransmitters
GABA ACH Dopamine Serotonin Epinephrine/Norepinephrine