1: Neurons and neurotransmission

Question 1

1. During the second half of the 19th century (between 1870 and 1900) two scientists have provided a relevant contribution on the understanding of neurons: who were they?

Answer 1

Camillo Golgi (Stain Method) and Santiago Ramon y Cajel (Identification of axon and synapses)

Question 2

2. Who demonstrated that nerves conduct electricity in 1791?

Answer 2

Lugi Galvani:

In a classical experiment, Galvani connected a nerve taken from a frog’s leg to a metallic wire. This was pointed to the sky during a thunderstorm (please notice that battery was invented about 10 years later by Volta) and it obtained muscular contraction of the frog’s leg.

Question 3

3.

Chemical Transmission

Who demonstrated that neurons communicate with each other by means of chemical transmission in 1921?

Answer 3

Otto Loewi

He placed two frog’s hearts in two different containers with a fluid.
He stimulated the vagus nerve (parasympathetic nerve) of one heart inducing the heartbeat to slow down.

He collected the fluid surrounding this heart and pouring it into the second container with the second unstimulated heart.

Then also the heartbeat of the second unstimulated heart start to slow down!

The “vagusstoff” (“vagus stuff”) was later identified as Acetylcholine

Question 4

4. Nerve communication is……………….?

Answer 4

Nerve communication is electrical!

Question 5

5. Synapses communication is ………………?

Answer 5

Synapses communication is chemical …and electrical!

Question 6

6. List the different mechanisms between eletrical and chemical synaptic transmission.

Answer 6

CHEMICAL synapses asymmetric morphology

• unidirectional
• slow (msec.)
• synaptic cleft
• divergence

ELECTRICAL synapses

• symmetric morphology
• bidirectional (each cell pre- or post-synaptic)
• fast (no delay)
• no synaptic cleft but gap junction (pores) in membranes
• synchronization role of large population of neurons (e.g. in retina12)

Question 7

7. Define action potential?

Answer 7

The change in electrical potential associated with the passage of an impulse along the membrane of a muscle cell or nerve cell.

Question 8

8. Draw a diagram illustrating the action potential being sent down the axon to the synaptic cleft.

Answer 8

Question 9

9. What does a neruon consist of?

Answer 9

A neuron consists of dendrites, a soma (body), axon and terminal buttons.

Question 10

10. Describe Terminal Buttons

Answer 10

The terminal buttons are located at the end of the neuron and are responsible for sending the signal on to other neurons. At the end of the terminal button is a gap known as a synapse. Neurotransmitters are used to carry the signal across the synapse to other neurons.

Question 11

11. Describe and draw a Cortical pyramidal cell

Answer 11

One of the main structural features of the pyramidal neuron is the triangular shaped soma, or cell body, after which the neuron is named. Other key structural features of the pyramidal cell are a single axon, a large apical dendrite, multiple basal dendrites, and the presence of dendritic spines.

Question 12

12. Describe and draw a retinal bipolar cell.

Answer 12

Bipolar cells are so-named as they have a central body from which two sets of processes arise. They can synapse with either rods or cones (but not both), and they also accept synapses from horizontal cells.

Question 13

13. Desribe and draw a Retinal Ganglion Cell

Answer 13

A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: horizontal cells and amacrine cells.

Question 14

14. Describe and draw a retinal amacrine cell.

Answer 14

There are about 22 different types of amacrine cells, most lacking axons. Like horizontal cells, amacrine cells work laterally affecting the output from bipolar cells, however, their tasks are often more specialized.

Question 15

15. Describe and draw a unipolar cell.

Answer 15

A unipolar neuron is a type of neuron in which only one protoplasmic process (neurite) extends from the cell body. Most neurons are multipolar, generating several dendrites and an axon and there are also many bipolar neurons.

Question 16

16. Describe and draw an example of a Cerebellar Purkinje Cell.

Answer 16

These cells are some of the largest neurons in the human brain (Betz cells being the largest), with an intricately elaborate dendritic arbor, characterized by a large number of dendritic spines. Purkinje cells are found within the Purkinje layer in the cerebellum.

Question 17

17. Which cells are more numerous than neurons?

Answer 17

Glial Cells (Glia) are much more common than neurons and they provide structural and chemical support to the neurons.

Question 18

18. What type of glia cell holds the neuron in place?

Answer 18

Astrocytes hold neurons in place, give nourishment to neurons and form the blood-brain barrier.

Question 19

19. Describe the Oligodendrocytes glia and draw a picture.

Answer 19

Oligodendrocytes provide myelin, which is an insulating covering around the axon.

Question 20

20. Describe microglia.

Answer 20

Microglia contribute to clean up from dead tissue and they are an important link with immune system.

Question 21

21. What is an ion?

Answer 21

An ion is an atom with different number of protons (+) and electrons (-). This result in a positive or negative charged ion.

Question 22

22. Ions distribution occurs according two general rules state them.

Answer 22

1. Electrostatic gradient: attraction/repulsion between different/similar charges
2. Osmotic balance or diffusion gradient: ions tend to spread around uniformly

Question 23

23. Extracellular and intracellular environments are very different in terms of ion concentration. Draw a diagram to illustrate this.

Answer 23

This results in a different electriacal charge. The inside is more negative than the outside.

Question 24

24. What is the resting potential?

Answer 24

The electrical potential of a neuron or other excitable cell relative to its surroundings when not stimulated or involved in passage of an impulse. Considering the outside as zero, the inside is –70mV

The charge difference (resting potential) is due to a different concentration of sodium (Na+), potassium (K+), Chloride (Cl-) and organic anions (A-).

Question 25

25. The charge difference (resting potentia) depends on which two mechanisms?

Answer 25

a) sodium-potassium pump that forces out sodium ions (NA+) (Gated channels)
b) membrane permeability that allows ions to move more or less easier in and out side (Non-gated channels)

Question 26

26. Describe Active transporters.

Answer 26

Active transport is the movement of molecules across a cell membrane in the direction against their concentration gradient, i.e. moving from a low concentration to a high concentration.

Question 27

27. Describe ion channels.

Answer 27

Ion channels are located within the plasma membrane of nearly all cells and many intracellular organelles. They are often described as narrow, water-filled tunnels that allow only ions of a certain size and/or charge to pass through. This characteristic is called selective permeability.

Question 28

28. List the mammalian neuron concentrations for intracellular and extracellular ions.

Answer 28

Question 29

29. When an axon is stimulated with …………………., its membrane becomes more permeable to ……….. (Na+) and ………….. (K+)

Answer 29

When an axon is stimulated with electric current, its membrane becomes more permeable to sodium (Na+) and potassium (K+)

Question 30

30. What happens after an axon’s membrane becomes more permiable?

Answer 30

sodium (Na+) and potassium (K+) move more freely across the membrane

mainly NA+ enters and K+ leaves the cell

Question 31

31. What is DEPOLARIZATION?

Answer 31

Depolarization is a positive-going change in a cell’s membrane potential, making it more positive, or less negative, and thereby removing the polarity that arises from the accumulation of negative charges on the inner membrane and positive charges on the outer membrane of the cell. In neurons and some other cells, a large enough depolarization may result in an action potential.

The charge difference between intracellular and extracellular environment is reduced towards 0 mV.

Question 32

32. Define resting potential.

Answer 32

• the potential difference between the two sides of the membrane of anerve cell when the cell is not conducting an impulse

Question 33

33. What is the refactory period?

Answer 33

The amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following excitation.

Question 34

34. Depolorisation is mainly due to what?

Answer 34

Depolarisation is mainly due to sodium (Na+) going inside the neuron.

Question 35

35. Repolorization is mainly due to what?

Answer 35

Restoring of resting potential (repolarization) is mainly due to potassium (K+) going outside

Question 36

36. Draw and label a bell curve illustrating a stimulation from resting potential to refactory period. Use mV on the y axis and Time on the x.

Answer 36

Question 37

37. Define Action Potential

Answer 37

When the stimulation is strong enough to produce a change over threshold we observe the
ACTION POTENTIAL (rapid depolarisation and repolarisation of membrane)

Question 38

38. Define Active Conduction

Answer 38

Because the action potential’s depolarization is localized, it is not able to conduct the current signal very far. Axons therefore provide a method, called active conduction, to maintain the current with undiminished intensity by way of repeated action potentials.

There are two forms of active conduction:

Unmyelinated Axons and myelinated Axons

Question 39

39. What is passive conduction?

Answer 39

Both passive potentials and active potentials propagate current in the intracellular fluid of the neuron.

The passive potential operates like a graded analog signal

• It decays with time and distance

For most neurons, passive conduction is not good enough to conduct the current signal all the way down the axon to the terminal boutons - Active conduction is needed.

Question 40

40. What is the “All-or-none law”

Answer 40

The origin of the axon (axon hillock) is the region of the neuron where excitatory and inhibitory postsynaptic potentials take place.

If the sum of these overcomes a specific threshold, then the action potential is generated (“All-or-none law”).

Question 41

41 Define SALTATORY CONDUCTION

Answer 41

Saltatory conduction (from the Latin saltare, to hop or leap) is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials.

Question 42

42. Where does the action potential occur?

Answer 42

Action potential occurs at each Node of Ranvier This speeds up the conduction of depolarisation

Question 43

43. Describe Frequency coding.

Answer 43

• Also known as rate coding.
• The rate coding model of neuronal firing communication states that as the intensity of a stimulus increases, the frequency or rate of action potentials, or “spike firing”, increases.

Question 44

44. Where do synapses occur and what is their role?

Answer 44

Synapses can occur on soma, dentrites or other axons

At the proximity of the dendritic spines, the synaptic vesicles release the neurotransmitters into the gap between pre- and post-synaptic membrane (synaptic cleft)

Question 45

45. How is the neurotransmitter released by the vesicles?

Answer 45

The action potential opens calcium channels located in the presynaptic membrane.

These bind with the protein embedded in the membrane of the synaptic vesicles.

The fusion pores widen and membrane of vesicle fuses with pre- synaptic membrane (“Omega figure”) and the neurotransmitter is released into the synaptic cleft.

Question 46

46. What happens after neurotransmitters are relased into the synaptic cleft?

Answer 46

The open vesicle can then closes again and be refilled with neurotransmitter or merges the presynaptic membrane.

While the neurotrasmitter binds with postsynaptic receptors (like a “lock and a key”)

…and then it is quickly deactivated.

Question 47

47. What are the key mechanisms for deactivating a neurotransmitter?

Answer 47

• Re-activating pumps that send back the neurotransmitter into the presynaptic membrane (e.g. Acetylcholinesterase)
• Broken-down or de-activation by enzymes
• By diffusion of the neurotransmitter away from the region of synapse

Question 48

48. Describe neurotransmitters and name the ones most relvant for the nervous system.

Answer 48

Today more than one hundred neurotransmitters have been recognised. The main relevant for nervous system are:

Noradrenaline (or Norepinephrine), dopamine, serotonin, GABA, acetylcoline and glutamate

Differences:
-Molecular structure, i.e. molecules vary in size and composition

Similarities:

• Synthesized by the presynaptic neuron
• Transported to the axon terminals to be stored in vesicles
• After binding with the postsynaptic membrane are removed or degraded.

Question 49

49. What helps a neruon define which neurotransmitter to release?

Answer 49

Neurons can release one, two or several different neurotransmitters together or separately and the type of neurotransmitter realised by a neuron depends on the rate of stimulation.

Question 50

50. What is a conditional neurotransmitter?

Answer 50

The neurotransmitter’s action is conditioned on the presence of another transmitter in the synaptic cleft

Question 51

51. List exitatory and inhibitory neurotransmitters.

Answer 51

Excitatory neurotransmitters are:

Acetylcholine (Ach), Catecolamine (i.e. Dopamine, Norepinephrine or Noradrenaline , Epinephrine), Glutamate, Histamine, Serotonine and other minor.

Inhibitory neurotransmitters are:

GABA, Glycine and other minor.

Question 52

52. What happens in the postsynaptic membrane when neurotransmitters bind with receptors?

Answer 52

A postsynaptic cell is continuously in contact with thousands of neurotransmitters.

The binding between neurotransmitter and receptors results in a permeability change of the postsynaptic membrane.

Question 53

53. Draw and label a diagram of glutamate receptors with reference to neuro placticity.

Answer 53

NMDA receptors are crucial in neuronal plasticity and memory process with calcium playing a fundamental role.

Question 54

54. Describe Long-term potentiation (LTP) & Long-term depression (LTD)

Answer 54

LTP is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously

LTD is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress.

Question 55

55. What have studies shown in synaptic activity that is of note when there is a weak signal followed by a strong one?

Answer 55

Synaptic activity of weak stimulus is potentiated by previous strong stimulus - LPT

Question 56

56. Name a brain area that has marked changes after induction of Long-term potentiation (LTP).

Answer 56

Hippocampal neuron dendrite before and after 120 minutes after induction of LTP.

Question 57

57. What happens to the resting potential if a cells permiability increases?

Answer 57

If cell’s permability increases for positive ions then the resting potential will become more positive

Question 58

58. Draw a table showing the properties of Axon and Dendrite.

Answer 58

Question 59

59. How do drugs affect neurotransmission?

Answer 59

They can interfere at different levels:

1) Synthesis of the neurotransmitter
2) Its storage in vesicles
3) Its release into the synapse
4) Reducing the ability to bind to receptor sites (antagonists)
5) Preventing re-uptake of the neurotransmitter (agonist)
6) De-activation of the neurotransmitter by enzymes

Question 60

60. Describe Mirror Neurons with a historical account.

Answer 60

• Mirror neurons are a particular class of visuomotor neurons, originally discovered in the monkey premotor cortex (F5).
• These neurons fire both when the monkey did a particular action and when it observed a similar action (Di Pellegrino et al. 1992, Gallese et al. 1996, Rizzolatti et al. 1996a).
• Thus, the neuron “mirrors” the behavior of another animal

Question 61

61. Discuss mirror neurons in humans.

Answer 61

Evidence of the existence of mirror neurons in human are only indirect (Neurophysiological and neuroimaging studies).

Altschuler et al. (1997, 2000) using EEG recordings
Hari et al. (1998) using magnetoencephalographic (MEG) technique. Individuals observe an action done by another individual, their motor cortex becomes active, in the absence of any overt motor activity.

Buccino et al. (2001) devised an fMRI study. Video clips showing transitive and intransitive actions compared to static similar pictures of hand/leg/mouth.

Mirror neurons in humans have been found in premotor cortex and parietal cortex of the brain