LESSON 2.3 WORKBOOK. How fast do our neurons signal?

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1 Glial cell several classes of non-neuronal cells of the nervous system. LESSON 2.3 WORKBOOK How fast do our neurons signal? Remember that winning goal you scored, that snowball you dodged or the cup of coffee you managed to catch before the cat knocked it all over your computer? Hundreds of times a day our quick reactions improve our performance or save us from disaster. Take a minute to think of something that happened to you this week. Often we react so quickly that we ve reacted before we even know what has happened. How can your neurons signal so quickly? In this lesson we will find out, and to do so we need to learn about the other important type of cell in our nervous systems the glial cell. Glial Cells There are actually far more glial cells (usually referred to as glia) than neurons in the CNS of vertebrates between 10 to 50 times more in fact. Nerve cell bodies and axons are surrounded by them and because of this they were named from the Greek word for glue. For a long time neuroscientists thought glial cells did behave like glue, and pretty much ignored them. Over the last few years though they have been found to be far more active than we thought, conducting their own signals and acting more as partners for neurons than the boring old structural cells we originally thought. Glia in fact have several vital roles in neuronal function: They provide firmness and structure to the brain. This isn t trivial. Remember from the lesson on neural imaging that the brain has very low density. Glia beef up the density and make the neurons more resistant to trauma. That s important because remember that if a brain neuron is damaged and dies it can t be replaced. Two different types of glial cells act as insulation, which as we shall see, allows the action potential to travel faster important if we want to move a signal quickly. When the brain is developing in the embryo, some glia act as guides so that the neural network forms its connections in the right place. What are glia cells, and what are some of their functions? Other glial cells help form an impermeable lining around the capillaries and venules of the brain that prevents toxic substances in the blood from entering the brain. This lining Lesson 2.3 is called the blood-brain barrier. 53

2 Nodes of Ranvier gaps between adjacent myelin segments on an axon. myelin insulating neurons. Myelination increases the conduction speed of the action potential In the last lesson we saw that if only one action potential occurred at the beginning of the axon, the depolarizing current wouldn t reach the axon terminal. This happens because as it travels down the axon some of the current leaks out of the axon across the membrane, and also because the materials in the axon (chiefly protein) offer resistance to the current. We also learned that some axons solve this problem by lining up their voltage-gated Na + channels along the axon membrane, so multiple action potentials can occur in rapid succession, ensuring that the signal is transmitted all the way down the axon. This is not a great solution because the energy required to keep the Na + /K + pump working to repolarize the axon membrane is huge. So axons have come up with another strategy, which is to have the action potential jump along the axon rather than progress down it (think of the action potential pogo-sticking down the axon rather than walking down). This how it works. Remember that the problem with a single action potential was that the current would decay. To prevent that decay glial cells wrap around the axon like beads on a necklace covering the axon tightly except for the areas in between the beads called nodes of Ranvier which remain naked axon (Figure 17). Two things make this strategy work. First the glia make a substance called myelin, which acts as an insulator. Now the parts of Figure 17: Nodes of Ranvier. Myelin is formed the axon that are wrapped around by the myelin from membranes of glial cells wrapping tightly are insulated and the depolarizing current can t around the axon, like beads on a necklace. Between the beads of myelin are spaces of naked leak out. Second the sodium channels are concentrated in the small areas of naked axon in axon, called the nodes of Ranvier. between each myelin bead so the action potential can hop down the axon like a pogo stick. Let s have a look in a bit more detail: Figure 18: Cross section of myelinated axons. The glial cell membranes wrap so tightly around the axon that the cytoplasm is squeezed out of the glial cells. The glial cells wrap around the axon like paper wrapping around a pencil. The glial cell membrane attaches so tightly to the axon, and to itself that there is no extracellular fluid in contact with the axon in that area (Figure 18). The only place where the axon comes into contact with extracellular fluid is at a node of Ranvier, where the axon is naked. In the myelinated areas therefore, there can be no inward flow of Na + into the How does myelination increase the conduction velocity of the action potential? axon because the myelin insulates the axon from the Lesson 2.3 extracellular fluid. 54

3 Saltatory conduction conduction of the action potential from one node of Ranvier to the next along a myelinated axon. How then does the action potential travel along the area of an axon covered by a myelin sheath? The answer to this is by behaving like an electrical cable. Since the axon is covered in myelin, there is minimal leakage of depolarizing charge out of the axon so the depolarizing current is able to travel passively between the nodes of Ranvier. When the depolarizing current reaches the next node of Ranvier, it encounters both Na + ions and Na + channels, and so it can trigger another action potential at the node. The action potential gets retriggered, or repeated, at each node of Ranvier and the depolarizing current moves passively along the myelinated portions of the axon to the next node. This type of conduction, which appears to hop from node to node, is called saltatory conduction, from the Latin saltare, to leap, to dance (Figure 19). Figure 20: Comparing action potential conduction in unmyelinated and myelinated axons. The black arrows represent current flowing down an unmyelinated axon and the red arrows represent current flowing down Why is myelination an advantage for the axon? We can immediately see two advantages of saltatory conduction. The first is it saves energy. Sodium ions that enter axons during the action potential must eventually be removed. You ll remember that the Na + ions are removed by Na + /K + pumps, which use significant amounts of energy. As we mentioned before, in axons that aren t myelinated, these pumps must be located along the entire length of the axon, because Na + ions can enter everywhere. However, in a myelinated axon, where Na + ions can only enter at the nodes of Ranvier, much less Na + gets in, and consequently, much less needs to be pumped out. Therefore, in myelinated axons much less energy is needed to remove Na + ions and maintain the high extracellular Na + concentration. The second advantage of myelin is speed. The action potential is conducted much faster in a myelinated axon because transmission between the nodes, which occurs by means of the axon s cable properties, is very fast (Figure 20). Increased speed enables us to react faster and undoubtedly to think faster. In fact, the fastest myelinated axon, 20 micrometers (µm) in What are the advantages of myelination? Think about your big toe neuron. Imagine the axon starts under your armpit. How long will an action potential take to travel down to your big toe if is myelinated? Lesson 2.3 a myelinated axon. Notice how diameter, can conduct action potentials at speeds of 150 m/s, 55 much faster the myelinated current travels. or 335 mph! Figure 19: Saltatory conduction. Action potentials are conducted down the myelinated axon via saltatory conduction. The depolarization jumps from one node to the next without decaying.

4 myelin insulating neurons. Saltatory conduction conduction of the action potential from one node of Ranvier to the next along a myelinated axon myelin insulating neurons Why aren t all neurons myelinated? Since myelin provides such important benefits decreasing energy consumption and increasing speed why aren t all of our axons myelinated? In fact, most of our axons are myelinated, but later we ll argue that having some unmyelinated axons is important. Take for example the so-called C fibers (fibers is just another name for nerve). C fibers are sensory neurons located in the PNS and involved in the pain response. They are not myelinated and their conduction velocities are slow 2 m/s (or only 4.5 mph). But conducting pain information slowly, gives us an advantage because we can respond to the source of the pain before the pain sensation becomes intense. Sometimes it is actually beneficial for a signal to reach our brains more slowly. What happens when myelin gets damaged? Demyelination is the loss of the myelin sheath insulating neurons. As you might imagine, losing even a part of the myelin sheath disrupts action potential conduction. When myelin is disrupted, conduction along an axon may become desynchronized or even fail completely. Demyelination is the hallmark of some neurodegenerative diseases including multiple sclerosis, (MS) and Charcot-Marie-Tooth disease. Demyelination results in a set of symptoms that will depend on which neurons are affected. We ll talk more about demyelinating diseases in the last lesson of this unit, but for now remember that the myelin sheath insulates the axon increasing the conduction velocity of the action potential, as well conserving the axon s energy. When does myelination occur? Under what circumstances would it be beneficial not to have myelinated axons? What if your big toe neuron wasn t myelinated? How long would it take the action potantial to reach your toe then? Would this be an advantage or not? At what age does our frontal lobe become myelinated? Recently, research has shown that our brains Mostly grey ma-er gradually add myelin as we mature. Figure 21 is taken from one of the studies on which that statement is based. Remember, grey matter is where Mostly white ma-er neurons connect with each other and white matter is where the myelinated axons are. The study analyzed changes in grey matter relative to white Figure 21: Loss of grey matter and gain of white matter from 5 20 years. Notice that our frontal matter, so another way to look at the data is that lobes are the last areas to become heavily myelinated and thus be represented as mostly white not only does grey matter decrease, but white matter also increases as we mature. Take a look matter. specifically our frontal lobes, which do not become fully myelinated until we are about 20. Some scientists have taken this further to argue that teenag- ers show poor judgment because their frontal lobes aren t fully myelinated. This conclusion has been hotly Lesson 2.3 debated in the field, and might be one you d like to take a minute to think about. 56

5 STUDENT RESPONSES Remember to identify your sources You just read about research that shows that the human brain, specifically the frontal lobe, is not heavily myelinated until the age of 20. Some scientists argue that teenagers show poor judgment because their brains aren t fully myelinated. What do you think? Do you agree with the scientists arguments? Do you think there could be another explanation? Lesson