1. Lecture 2 Neurons and Action Potentials

2. Anatomy of Neurons and Glia
The human nervous system is comprised of two kinds of cells:
Neurons
Glia
The human brain contains approximately 100 billion individual neurons

3. Figure 2-1 here and caption
Figure 2.1: Estimated numbers of neurons in humans.
Because of the small size of many neurons and the variation in cell density from one spot to another, obtaining an accurate count is difficult. (Source: R. W. Williams & Herrup, 1988)

4. Anatomy of Neurons and Glia (cont’d.)
In the late 1800s, the Spaniard Santiago Ramon y Cajal ( ) was the first to demonstrate that the individual cells comprising the nervous system remained separate
He showed that they did not grow into each other as previously believed

5. Anatomy of Neurons and Glia (cont’d.)
Like other cells in the body, neurons contain the following structures:
Membrane
Nucleus
Mitochondria
Ribosomes
Endoplasmic reticulum

6. Figure 2.2: An electron micrograph of parts of a neuron from the cerebellum of a mouse.
The nucleus, membrane, and other structures are characteristic of most animal cells. The plasma membrane is the border of the neuron. Magnification approximately x 20,000. (Source: Micrograph courtesy of Dennis M. D. Landis)

7. Anatomy of Neurons and Glia (cont’d.)
The membrane: a structure that separates the inside of the cell from the outside environment
The nucleus: a structure that contains the chromosomes
The mitochondrion: structure that performs metabolic activities and provides energy that the cells requires

8. Anatomy of Neurons and Glia (cont’d.)
Ribosomes: sites at which the cell synthesizes new protein molecules
Endoplasmic reticulum: network of thin tubes that transport newly synthesized proteins to their location

9. Anatomy of Neurons and Glia (cont’d.)
Figure 2.3: The membrane of a neuron.
Embedded in the membrane are protein channels that permit certain ions to cross through the membrane at a controlled rate.

10. Anatomy of Neurons and Glia (cont’d.)
Neuron cells are similar to other cells of the body but have a distinctive shape
A motor neuron has its soma in the spinal cord and receives excitation from other neurons and conducts impulses along its axon to a muscle
A sensory neuron is specialized at one end to be highly sensitive to a particular type of stimulation (touch, light, sound, etc.)

11. Anatomy of Neurons and Glia (cont’d.)
Figure 2.4: Neurons, stained to appear dark.
Note the small fuzzy-looking spines on the dendrites.

12. Anatomy of Neurons and Glia (cont’d.)
Figure 2.5: The components of a vertebrate motor neuron.
The cell body of a motor neuron is located in the spinal cord. The various parts are not drawn to scale; in particular, a real axon is much longer in proportion to the soma.

13. Anatomy of Neurons and Glia (cont’d.)
Figure 2.6: A vertebrate sensory neuron.
Note that the soma is located on a stalk off the main trunk of the axon. (As in Figure 2.5, the various structures are not drawn to scale.)

14. Anatomy of Neurons and Glia (cont’d.)
All neurons have the following major components:
Dendrites
Soma/cell body
Axon
Presynaptic terminals

15. Anatomy of Neurons and Glia (cont’d.)
Dendrites are branching fibers with a surface lined with synaptic receptors responsible for bringing information into the neuron
Some dendrites also contain dendritic spines that further branch out and increase the surface area of the dendrite
The greater the surface area of the dendrite, the more information it can receive

16. Anatomy of Neurons and Glia (cont’d.)
Figure 2.7: Dendritic spines.
The dendrites of certain neurons are lined with spines, short outgrowths that receive specialized incoming information. That information apparently plays a key role in long-term changes in the neuron that mediate learning and memory. (Source: From K. M. Harris and J. K. Stevens, Society for Neuroscience, “Dendritic spines of CA1 pyramidal cells in the rat hippocampus: Serial electron microscopy with reference to their biophysical characteristics.” Journal of Neuroscience, 9, 1989, 2982–2997. Copyright © 1989 Society for Neuroscience. Reprinted by permission.)

17. Anatomy of Neurons and Glia (cont’d.)
Cell body/soma: contains the nucleus, mitochondria, ribosomes, and other structures found in other cells
Also responsible for the metabolic work of the neuron

18. Anatomy of Neurons and Glia (cont’d.)
Axon: thin fiber of a neuron responsible for transmitting nerve impulses toward other neurons, organs, or muscles
Some neurons are covered with an insulating material called the myelin sheath with interruptions in the sheath known as nodes of Ranvier

19. Anatomy of Neurons and Glia (cont’d.)
Presynaptic terminals refer to the end points of an axon where the release of chemicals to communicate with other neurons occurs

20. Anatomy of Neurons and Glia (cont’d.)
Terms used to describe the neuron include the following:
Afferent axon: refers to bringing information into a structure
Efferent axon: refers to carrying information away from a structure
Interneurons or intrinsic neurons are those whose dendrites and axons are completely contained within a single structure

21. Anatomy of Neurons and Glia (cont’d.)
Figure 2.8: Cell structures and axons.
It all depends on the point of view. An axon from A to B is an efferent axon from A and an afferent axon to B, just as a train from Washington to New York is exiting Washington and approaching New York.

22. Anatomy of Neurons and Glia (cont’d.)
Neurons vary in size, shape, and function
The shape of a neuron determines it connection with other neurons and contribution to the nervous system
The function is closely related to the shape of a neuron
Example: Pukinje cells of the cerebellum branch extremely widely within a single plane

23. Figure 2.9: The diverse shapes of neurons.
(a) Purkinje cell, a cell type found only in the cerebellum; (b) sensory neurons from skin to spinal cord; (c) pyramidal cell of the motor area of the cerebral cortex; (d) bipolar cell of retina of the eye; (e) Kenyon cell, from a honeybee. (Source: Part e, from R. G. Coss, Brain Research, October Reprinted by permission of R. G. Coss.)

24. Anatomy of Neurons and Glia (cont’d.)
Glia (or neuroglia) are the other major components of the nervous system
Types of glia in the brain:
Astrocytes help synchronize the activity of the axon by wrapping around the presynaptic terminal and taking up chemicals released by the axon
Microglia remove waste material and other microorganisms that could prove harmful to the neuron

25. Anatomy of Neurons and Glia (cont’d.)
(Types of glia continued)
Oligodendrocytes (in the brain and spinal cord) and Schwann cells (in the periphery of the body) build the myelin sheath that surrounds and insulates certain vertebrate axons
Radial glia guide the migration of neurons and the growth of their axons and dendrites during embryonic development

26. Anatomy of Neurons and Glia (cont’d.)
When embryonic development finishes, most radial glia differentiate into neurons and a smaller number differentiate into astrocytes and oligodendrocytes

27. Figure 2.10: Shapes of some glia cells.
Oligodendrocytes produce myelin sheaths that insulate certain vertebrate axons in the central nervous system; Schwann cells have a similar function in the periphery. The oligodendrocyte is shown here forming a segment of myelin sheath for two axons; in fact, each oligodendrocyte forms such segments for 30 to 50 axons. Astrocytes pass chemicals back and forth between neurons and blood and among neighboring neurons. Microglia proliferate in areas of brain damage and remove toxic materials. Radial glia (not shown here) guide the migration of neurons during embryological development. Glia have other functions as well.

28. Figure 2.11: How an astrocyte synchronizes associated axons.
Branches of the astrocyte (in the center) surround the presynaptic terminals of related axons. If a few of them are active at once, the astrocyte absorbs some of the chemicals they release. It then temporarily inhibits all the axons to which it is connected. When the inhibition ceases, all of the axons are primed to respond again in synchrony. (Source: Based on Antanitus, 1998)

29. The Blood-Brain Barrier
The blood-brain barrier is a mechanism that surrounds the brain and blocks most chemicals from entering
The immune system destroys damaged or infected cells throughout the body
Because neurons in the brain generally do not regenerate, it is vitally important for the blood brain barrier to block incoming viruses, bacteria, or other harmful material from entering

30. Figure 2.12: The blood-brain barrier.
Most large molecules and electrically charged molecules cannot cross from the blood to the brain. A few small, uncharged molecules such as O2 and CO2 cross easily; so can certain fat-soluble molecules. Active transport systems pump glucose and amino acids across the membrane.

31. The Blood-Brain Barrier (cont’d.)
Active transport is the protein-mediated process that expends energy to pump chemicals from the blood into the brain
Glucose, certain hormones, amino acids, and a few vitamins are brought into the brain via active transport
The blood-brain barrier is essential to health, but can pose a difficulty in allowing chemicals such as chemotherapy for brain cancer to pass the barrier

32. Nourishment in Vertebrate Neurons
Vertebrate neurons depend almost entirely on glucose: a sugar that is one of the few nutrients that can pass through the blood-brain barrier
Neurons need a steady supply of oxygen; 20% of all oxygen consumed by the body is used by the brain

33. Nourishment in Vertebrate Neurons (cont’d.)
The body needs a vitamin, thiamine, to use glucose
Prolonged thiamine deficiency leads to death of neurons as seen in Korsakoff’s syndrome, a result of chronic alcoholism
Korsakoff’s syndrome is marked by severe memory impairment

34. The Nerve Impulse
A nerve impulse is the electrical message that is transmitted down the axon of a neuron
The impulse does not travel directly down the axon but is regenerated at points along the axon so that it is not weakened
The speed of nerve impulses ranges from less than 1 meter/second to 100 meters/second
A touch on the shoulder reaches the brain more quickly than a touch on the foot

35. The Nerve Impulse (cont’d.)
The brain is not set up to register small differences in the time of arrival of touch messages
It does matter with vision where movements must be detected as accurately as possible
The properties of impulse control are well adapted to the exact needs for information transfer in the nervous system

36. The Resting Potential of the Neuron
The membrane of a neuron maintains an electrical gradient
A difference in the electrical charge inside and outside of the cell
This is also known as polarization

37. The Resting Potential of the Neuron (cont’d.)
At rest, the membrane maintains an electrical polarization or a difference in the electrical charge of two locations
The inside of the membrane is slightly negative with respect to the outside (approximately -70 millivolts)
The resting potential of a neuron refers to the state of the neuron prior to the sending of a nerve impulse

38. Figure 2.13: Methods for recording activity of a neuron.
(a) Diagram of the apparatus and a sample recording. (b) A microelectrode and stained neurons magnified hundreds of times by a light microscope.

39. The Resting Potential of the Neuron (cont’d.)
The membrane is selectively permeable, allowing some chemicals to pass more freely than others
Sodium, potassium, calcium, and chloride pass through channels in the membrane
When the membrane is at rest:
Sodium channels are closed
Potassium channels are partially closed allowing the slow passage of potassium

40. The Resting Potential of the Neuron (cont’d.)
Figure 2.14: Ion channels in the membrane of a neuron.
When a channel opens, it permits one kind of ion to cross the membrane. When it closes, it prevents passage of that ion.

41. The Resting Potential of the Neuron (cont’d.)
The sodium-potassium pump is a protein complex that continually pumps three sodium ions out of the cells while drawing two potassium ions into the cell
Helps to maintain the electrical gradient

42. The Resting Potential of the Neuron (cont’d.)
The electrical gradient and the concentration gradient (the difference in distributions of ions) work to pull sodium ions into the cell
The electrical gradient tends to pull potassium ions into the cells, but they slowly leak out, carrying a positive charge with them

43. Figure 2.15: The sodium and potassium gradients for a resting membrane.
Sodium ions are more concentrated outside the neuron; potassium ions are more concentrated inside. Protein and chloride ions (not shown) bear negative charges inside the cell. At rest, very few sodium ions cross the membrane except by the sodium-potassium pump. Potassium tends to flow into the cell because of an electrical gradient but tends to flow out because of the concentration gradient.

44. The Action Potential
The resting potential remains stable until the neuron is stimulated
Hyperpolarization refers to increasing the polarization or the difference between the electrical charge of two places
Depolarization refers to decreasing the polarization towards zero
The threshold of excitement refers to a level above which any stimulation produces a massive depolarization

45. The Action Potential (cont’d.)
An action potential is a rapid depolarization of the neuron
The action potential threshold varies from one neuron to another
Stimulation of the neuron past the threshold of excitation triggers a nerve impulse or action potential

46. The Action Potential (cont’d.)
Voltage-activated channels are membrane channels whose permeability depends upon the voltage difference across the membrane
Sodium and potassium channels are voltage activated channels
When sodium channels are opened, positively charged sodium ions rush in and a subsequent nerve impulse occurs

47. Figure 2.16: The movement of sodium and potassium ions during an action potential.
Sodium ions cross during the peak of the action potential and potassium ions cross later in the opposite direction, returning the membrane to its original polarization.

49. The Action Potential (cont’d.)
After an action potential occurs, sodium channels are quickly closed
The neuron is returned to its resting state by the opening of potassium channels
Potassium ions flow out due to the concentration gradient and take with them their positive charge
The sodium-potassium pump later restores the original distribution of ions

50. The Action Potential (cont’d.)
The process of restoring the sodium-potassium pump to its original distribution of ions takes time
An unusually rapid series of action potentials can lead to a build up of sodium within the axon
Can be toxic to a cell, but it only occurs in rare instances such as stroke and after the use of certain drugs

51. The Action Potential (cont’d.)
Local anesthetic drugs block sodium channels and therefore prevent action potentials from occurring
Example: Novocain and Xylocaine

52. The Action Potential (cont’d.)
Once an action potential starts, it can back-propagate into the cell body and dendrites, causing the dendrites to be more susceptible to structural changes responsible for learning
The all-or-none law states that the amplitude and velocity of an action potential are independent of the intensity of the stimulus that initiated it
Action potentials are equal in intensity and speed within a given neuron

53. The Action Potential (cont’d.)
Action potentials vary from one neuron to another in terms of amplitude, velocity, and shape
Studies of mammalian axons show that there is much variation in the types of protein channels and therefore in the characteristics of the action potentials

54. The Action Potential (cont’d.)
After an action potential, a neuron has a refractory period during which time the neuron resists the production of another action potential
The absolute refractory period is the first part of the period in which the membrane cannot produce an action potential
The relative refractory period is the second part in which it takes a stronger than usual stimulus to trigger an action potential

55. Propagation of the Action Potential
In a motor neuron, the action potential begins at the axon hillock (a swelling where the axon exits the soma)
Propagation of the action potential is the term used to describe the transmission of the action potential down the axon
The action potential does not directly travel down the axon

56. Figure 2.17
Current that enters an axon during the action potential flows down the axon, depolarizing adjacent areas of the membrane. The current flows more easily through thicker axons. Behind the area of sodium entry, potassium ions exit.

57. The Myelin Sheath and Saltatory Conduction
The myelin sheath of axons are interrupted by short unmyelinated sections called nodes of Ranvier
Myelin is an insulating material composed of fats and proteins
At each node of Ranvier, the action potential is regenerated by a chain of positively charged ion pushed along by the previous segment

58. Figure 2.18: An axon surrounded by a myelin sheath and interrupted by nodes of Ranvier.
The inset shows a cross-section through both the axon and the myelin sheath. Magnification approximately x 30,000. The anatomy is distorted here to show several nodes; in fact, the distance between nodes is generally about 100 times as large as the nodes themselves.

59. The Myelin Sheath and Saltatory Conduction (cont’d.)
Saltatory conduction: used to describe the “jumping” of the action potential from node to node
Provides rapid conduction of impulses
Conserves energy for the cell
Multiple sclerosis: disease in which the myelin sheath is destroyed and associated with poor muscle coordination and sometimes visual impairments

60. The Myelin Sheath and Saltatory Conduction (cont’d.)
Figure 2.19: Saltatory conduction in a myelinated axon.
An action potential at the node triggers flow of current to the next node, where the membrane regenerates the action potential.

61. Local Neurons Not all neurons have lengthy axons
Local neurons have short axons, exchange information with only close neighbors, and do not produce action potentials
When stimulated, local neurons produce graded potentials, which are membrane potentials that vary in magnitude and do not follow the all-or-none law
A local neuron depolarizes or hyperpolarizes in proportion to the stimulation

62. Local Neurons (cont’d.)
Local neurons are difficult to study due to their small size
Most of our knowledge has come from the study of large neurons