1. Neurons
A nerve cell capable of generating and transmitting electrical signals
Vary in structure and properties
Use the same basic mechanisms to send signals
Generate action potentials or passive potential
Communicate with other neurons or cells via synaptic connections (electrical or chemical)
This is a sample first topic page.

2. Neurons
This is a sample first topic page.

3. Structural Diversity of Neurons

4. Neuron Classification Based on Structure

5. Neuron Classification Based on Function

6. Neural Zones Four functional zones
Signal reception: dendrites and the cell body (soma)
- Incoming signal is received and converted to a change in membrane potential
Signal integration: axon hillock
- Strong signal  action potential (AP)
Signal conduction: axon; some wrapped in myelin sheath
- AP travels down axon
Signal transmission: axon terminals
- Neurotransmitter is released

7. Neural Zones, Cont.

8. Electrical Signals in Neurons
Neurons have a resting membrane potential (like all cells)
Neurons are excitable; can rapidly change their membrane potential
Changes in membrane potential act as electrical signals

9. Measuring the voltage
Use microelectrodes to measure the voltage between outside and inside
Conducting fluid such as KCL is used
Reference electrode is placed in the bathing medium
Potentiometer will measure the potential ie
resting potential

10. Three factors contribute to the membrane potential
The distribution of ions across the plasma membrane
The relative permeability of the membrane to these ions
The charges of the ions
►Nernst equation can be used to measure the potential of a cell ie the voltage difference between the inside and the outside of the cell.

11. Membrane Potential
EK+ = (1.9872*295)/(1*23062) ln (4/139) = - 88 mV at 22oC
ENa+ = (1.9872*295)/(1*23062) ln (145/12) = 62 mV at 22oC
ECl- = (1.9872*295)/(-1*23062) ln (116/4) = - 84 mV at 22oC

12. Resting potential
Origin of the resting potential in a typical vertebrate neuron.
A- - negatively charged proteins
Resting neuron: 10 times more open K+ channels than Na+ or Cl- channels
Outside of cell is more positive relative to the inside of the cell
K+ is dominant because its permeability is greatest (PK). This is due to leak channels
So the resting potential is closest to the Nernst potential for K+
Also have leakage of Na+ (PNa) and Cl- (PCl)

13. Resting potential Actual measurements of membrane potential
Measured in giant axon of squid
Found resting potential of -65 to -70 mV
Increased external K+ to determine new membrane potential
Found a slope of – 58 mV ► means that for every ten fold increase in external K+ the potential will increase by 58 mV at room temperature
So other ions are influencing the resting potential!!
Permeability of Na+ and Cl- ions and the presence of proteins.
Use Goldman equation to calculate the resting potential

14. Resting potential

15. Membrane Potential In the giant squid:
Nernst equation predicts membrane potential for a single ion
Goldman equation for the membrane potential (Em): predicts the membrane potential using multiple ions
Chloride ion has a charge opposite to the two cations, a correction is needed
to prevent the cations and anion from canceling each other.
Thus, the statement of relative chloride ion concentrations is inverted—
inside over outside
In the giant squid:
PK+ : PNa+ : PCl- = 1 : 0.04 : 0.45

16. Membrane Potential Effects of changing the ion permeability
The resting membrane potential is -53 mV; ENa, EK, and ECl are the potentials
calculated from the Nernst equation if the membrane contains only open channels for
Na+ or K+ or Cl-, respectively.

17. Electrical signals
Changes in Channel permeability create Electrical signals!
Mechanically gated ion channels
Sensory neurons. Open in response to pressure or stretch
Chemically gated ion channels
Respond to ligands
Voltage gated Na+ channels
Respond to changes in membrane potential
Voltage gated K+ channels or CA2+ channels

18. Graded Potential vs. Action Potential
Two types of electrical signals

19. Action potentials Active conduction
Passive conduction of signal is limited by properties of the nerve and signal is reduced over distance
Active conduction ie action potentials (AP)
- Signal travels along nerve with no loss of amplitude

20. Action Potentials (AP)
Occurs only when the membrane potential at the axon hillock reaches threshold
Three phases
Depolarization
Repolarization
Hyperpolarization
Absolute refractory period – incapable of generating a new AP
Relative refractory period – more difficult to generate a new AP

21. Voltage-Gated Channels
Change shape due to changes in membrane potential
Positive feedback, e.g., influx of Na+   local depolarization   number of open Na+ channels
Na+ channels open first (depolarization)
K+ channels open more sloooooowly (repolarization)
Na+ channels close
K+ channels close slooooowly (relative refractory period)

22. Channels of an Action potentials
Voltage gated Na+ channels:
3 states: closed, open, inactive
Closed to open:
Depolarization is necessary to open the channel
Acts to activate itself in a regenerative cycle
More Na+ influx depolarizes the membrane which opens more channels which depolarizes the membrane more.
Open to Inactive:
Depolarization is also necessary to inactive the channel
Once the channel is open it will then also switch to the inactive state and can not be opened again
Inactive to closed:
The channel will not switch back to the closed state until the membrane has repolarized (i.e. gone back towards the original resting membrane potential
Once in the closed state it can then be reopened

23. Na+ Channels Have Two Gates
Activation gate – voltage dependent
Inactivation gate – time-dependent

24. Na+ Channels Have Two Gates

25. Channels of an Action potentials
Voltage gated K+ channels (delayed rectifying K+ channel):
2 states: closed and open
Closed to open:
Strong depolarization is necessary to open the channel
Hyperpolarizes the cell
Brings membrane back towards Nernst potential for K+
Open to Closed:
Will close when the membrane becomes hyperpolarized
Works to shut itself down

26. Voltage-Gated Channels, step by step

27. Action Potentials Travel Loooong Distances
“All-or-none” – occurs or does not occur; identical without degradation
Self propagating - an AP triggers the next AP in adjacent areas of the axonal membrane
Electronic current spread in between ion channels
Cycle: Ion entry  electronic current spread  triggering AP

28. Components of an Action potentials

29. Components of an Action potentials
Threshold
Most neurons have a threshold at -50 mV (i.e. 10 to 15 mV depolarization)
Action potential is an all or none event. If a nerve is at rest the amplitude
on one action potential will be the same all along the nerve independent of the
stimulus strength
Threshold reflects the need to trigger the opening of the voltage-gated
sodium channel (need a depolarization of about 10 to 15 mV to open)
Rising phase
Sodium channels open
Na+ ions flow into cell
Depolarizes the cell
More and more sodium channels open
= a regenerative response
regenerative opening of sodium
channels drives the membrane potential
towards a peak of the Nernst equilibrium
potential for Na+

30. Components of an Action potentials
Peak
During an action potential the membrane potential goes towards the
Nernst equilibrium potential for Na+
In terms of Goldman-Katz equation now permeability to Na+ is dominant
(K+ and Cl- minor components) therefore membrane potential goes towards
ENa
Usually falls short of ENa, less driving force on Na+ and the channels begin
to inactivate rapidly after activation

31. Components of an Action potentials
Fall
Membrane potential falls back towards rest - Why doesn't the action potential stay around ENa? Two reasons: i) Na+ channels move into an inactive state ii) delayed K+ channels open  
Inactivating Na+ channels - Na+ channels go to an inactivated state after 1-2 msec after first opening - inactivated = can NOT be reopened - Membrane potential now determined mostly by K+
(same as for resting potential) and membrane starts to repolarize
Delayed K+ channels open (delayed rectifier; voltage-gated like Na+ channel) - open after about 1-2 msec of threshold depolarization - now K+ flows out of the cell and speeds the repolarization process - cause the hyperpolarization after the action potential
- open K+ channels make the K+ permeability higher than at rest
- membrane more negative on inside
- hyperpolarization of membrane causes K+ channels to close - Membrane settles back to rest

32. Components of an Action potentials
Repolarization
Voltage-gated Na+ channels and voltage-gated K+ channels now closed
Membrane goes back to the resting state - i.e. the leak channels are the only channels open and again
set the membrane potential  

33. Unidirectional Signals
Stimulus starts at the axon hillock and travels towards the axon terminal
Up-stream Na+ channels (just recently produced an AP) are in the absolute refractory period
The absolute refractory period prevents backward transmission and summation of APs
Relatively refractory period also contributes by requiring a very strong stimulus to cause an AP

34. Refractory period (RP)
Absolute RP
Na+ channels are inactive and CAN NOT be opened no matter how much
the membrane is depolarized at this time
another action potential can not be generated
Relative RP 
Membrane repolarizes ----
goes to more negative potentials
Triggers the Na+ channels to move
from an inactive state to a close state
Hyperpolarization by the opening of the
K+ channels
Once Na+ channel is in the closed state
it can be opened again with depolarization
during relative RP, more and more
Na+ channels available to be opened and
therefore increase the chances of firing
an action potential

35. Refractory period (RP)

36. Frequency of AP
How does a nerve communicate the strength of a stimulus?
Information is given by the frequency of the AP along the nerve
Stimulus strength triggers different frequency of AP
For example: light touch – infrequent AP;
rough touch – more frequent AP
Refractory period limits the frequency of AP
During the relative RP an AP can be generated
but has to be at supra threshold because it has to
overcome the hyperpolarization
Will be at decreased amplitude because
fewer Na+ channels are available to open

37. Direction of AP
Unidirectional conduction of an action potential due to transient
inactivation of voltage-gated Na+ channels

38. Action Potentials Travel Loooong Distances
Triggered by the net graded potential at the axon hillock (trigger zone)
Do not degrade
Travel looong distances
All-or-none
Must reach threshold potential to fire

39. Action Potentials Travel Looong Distances

40. Action Potentials Travel Looong Distances

41. Signals in the Dendrites and Cell Body
Incoming signal, e.g., neurotransmitter
Membrane-bound receptors transduce the chemical signal to an electrical signal by changing the membrane potential (graded potential)

42. Graded Potentials
Vary in magnitude depending on the strength of the stimulus
e.g., more neurotransmitter  more ion channels will open

43. Graded Potentials Ions move down an electrochemical gradient
Net movement stops when the equilibrium potential is reached
Can depolarize (Na+ and Ca2+ channels) or hyperpolarize (K+ and Cl- channels) the cell

44. Graded Potentials Travel Short Distances
Conduction with decrement –  strength with  distance from opened ion channel
Due to
Leakage of charged ions across the membrane
Electrical resistance of the cytoplasm
Electrical properties of the membrane
Electrotonic current spread – positive charge spreads through the cytoplasm causing depolarization of the membrane
Can be excitatory or inhibitory

45. Graded Potentials Travel Short Distances

46. Integration of Graded Signals
Many graded potentials can be generated simultaneously
Many receptor sites
Many kinds of receptors
Temporal summation – graded potentials that occur at slightly different times can influence the net change
Spatial summation – graded potentials from different sites can influence the net change

47. Spatial summation

48. Temporal summation

49. Integration of Graded Signals, Cont.

50. Back to Neuron structure

51. Myelination Vertebrate neurons are myelinated
Myelin – insulating layer of lipid-rich Schwann cells wrapped around the axon
Glial cells – supportive neural cells, e.g., Schwann cells

52. Myelination, Cont.

53. Myelination, Cont.
Nodes of Ranvier – areas of exposed axonal membrane in between Schwann cells
Internodes – the myelinated region
Saltatory conduction – APs “leap” from node to node; APs at nodes of Ranvier and electrotonic current spread through internodes

54. Myelinated Neurons in Vertebrates
Disadvantage of large axons
Take up a lot of space which limits the number of neurons that can be packed into the nervous system
Have large volumes of cytoplasm making them expensive to produce and maintain
Myelin enables rapid signal conduction in a compact space

55. Myelin Increases Conduction Speed
 membrane resistance: act as insulators   current loss through leak channels   membrane resistance   l
 capacitance:  thickness of insulating layer   capacitance   time to constant of membrane   conduction speed
Nodes of Ranvier are needed to boost depolarization

56. Glial Cells Most neural cells (90% in human brain) Cannot generate APs
Five main types
Schwann cell – form myelin in motor and sensory neurons of the PNS
Oligodendrocyte – form myelin in the CNS
Astrocyte – transport nutrients, remove debris in CNS
Microglia – Remove debris and dead cells from CNS
Ependymal cells – line the fluid-filled cavities of the CNS

57. Conduction Speed
Two ways to increase speed: myelin and increasing the diameter of the axon

58. Cable Properties
Similar physical principals govern current flow through axons and telephone cables
Current (I) – amount of charge moving past a point at a given time
A function of the drop in voltage (V) across the circuit and the resistance (R) of the circuit
Voltage – energy carried by a unit charge
Resistance – force opposing the flow of electrical current
Ohm’s law: V = IR

59. Cable Properties, Cont.
Ions moving through voltage-gated channels cause a current across the membrane
Current spreads electrotonically
Some current leaks out of the axon, and flows backwards along the outside of the axon, completing the circuit

60. Cable Properties, Cont.
Each area of axon consists of an electrical circuit
Three resisters: extracellular fluid (Re), the membrane (Rm), and the cytoplasm (Rc)
A capacitor (Cm) – stores electrical charge; two conducting materials (ICF and ECF) and an insulating layer (phospholipids)

61. Voltage Decreases With Distance
Conduction with decrement
Due to resistance
Intracellular fluid: high resistance   decrement
Extracellular fluid: high resistance   decrement
Membrane: high resistance   decrement
K+ leak channels (always open): some + charge leaks out   current
Few K+ leak channels   + charge leak out  high membrane resistance

62. Length Constant (l)
Distance over which change in membrane potential will decrease by 37% (1/e)
ro is usually low and constant
l is largest when rm is high and ri is low

63. Speed of Conduction and Resistance
Axonal conduction is a combination of electrotonic current flow and APs
Electrotonic current flow is much faster than APs
But, electronic current flow is graded and can travel only short distances
Greater l  more electrotonic current flow

64. Speed of Conduction and Capacitance
Capacitance – quantity of charge needed to create a potential difference between two surfaces of a capacitor
Depends on three features of the capacitor
Material properties: generally the same in cells
Area of the two conducting surfaces:  area   capacitance
Thickness of the insulating layer:  thickness   capacitance

65. Speed of Conduction and Capacitance
Time constant (t) - time needed to charge the capacitor; t = rmcm
Low rm or cm  low t  capacitor becomes full faster  faster depolarization  faster conduction

66. Giant Axons
Easily visible to the naked eye
Not present in mammals

67. Giant Axons Have High Conduction Speed
rm is inversely proportion to surface area:  diameter   surface area   leak channels   resistance
ri is inversely proportional to volume:  diameter   volume   resistance
Effect of resistance
 rm   l   conduction speed
 ri   l   conduction speed
Do not cancel each other out: rm is proportional to radius, ri is proportional to radius2
Therefore, net effect of increasing radius of the axon is to increase the speed of conduction

68. Giant Axons Have High Conduction Speed