Why do large neurotransmitters travel faster down the axon?

I understand that with large neurotransmitters, like neuropeptides, the precursor neurotransmitter and the enzymes are produced in the soma and quickly travel down the axon to be modified in the axon terminal.

With the small molecule transmitters, the enzymes are made in the soma and then transported slowly down the terminal to the terminal where they synthesize the small transmitters.

Why is it that the precursors and enzymes for large neurotransmitters travel fast down the axon, whereas the enzymes for the small transmitters travel slowly? Is there a specific reason?

I presume you are referring to fast versus slow axoplasmic transport.

I presume by "small neurotransmitters," you are referring to "small molecule" neurotransmitters like GABA, glutamate, acetylcholine, and the catecholamines like dopamine.

For the "large" neurotransmitters, I assume you are referring to peptides.

(for a quick reference on these two categories you can see this book blurb)

Although local protein synthesis is possible outside the soma, particularly in dendrites, and there is even evidence for protein synthesis in axons, including neurotransmitter peptides, most protein synthesis still seems to occur in the vicinity of the nucleus, at the soma. Synthesis anywhere else means you need to transport the mRNAs and translation machinery instead, since the mRNA needs to be made at the nucleus. Even the "large" neurotransmitters, which are peptides, need to be synthesized just like bigger proteins.

Back to axoplasmic transport… There are two main mechanisms for moving things down the axon. The faster version of this transport is really for the transport of vesicles. To transport a neurotransmitter peptide in this fashion, you fill a vesicle full of the peptide and send it on its way along the microtubules via kinesin and dynein motors.

Larger, non-membrane bound proteins, however, are often not transported in vesicles, but by the slower transport mechanism. Note that this transport is still pretty fast, way faster than simple diffusion, it just isn't as fast as the "fast" transport. The exact mechanisms of slow transport are still an active area of research and not fully understood.

To get back to your question, "is there a specific reason?" The reason isn't so much about the speed, but about the mechanism of transport. Small peptides and membrane-bound proteins move in vesicles via fast transport. Large proteins not bound in membranes move via slow transport. The enzymes that synthesize the small neurotransmitters fall into this latter category. Importantly, although the neurotransmitters may be small, the enzymes themselves can be big, at least certainly bigger than the small peptides that are equivalent to the "large" neurotransmitters.

The Nervous System

First, the autonomic nervous system regulates the internal environment in an individual and controls functions that can be inhibited to provide or conserve energy appropriate to the environmental needs of the person. This system is involuntary. It is important to note that control of the body’s internal environment is not an all-or-none affair. In order to maintain the balance we have two divisions of the autonomic nervous system the sympathetic division, and the parasympathetic division.
The sympathetic nervous system kicks into gear when energy expenditure is necessary (ex: during times of stress or excitement). Because of this, it has earned the nickname the “fight or flight response”. This system can do things such as increase heart rate and blood pressure, stimulate secretion of adrenaline, and increase blood flow to skeletal muscles.
The parasympathetic nervous system returns our body back to homeostasis. It kicks in when energy reserves can be conserved and saved for later use. This system is capable of increasing salivation, digestion, and storage of glucose and it can slow down heart rate as well as decrease respiration.

Neuronal Communication

Now that we have learned about the basic structures of the neuron and the role that these structures play in neuronal communication, let’s take a closer look at the signal itself—how it moves through the neuron and then jumps to the next neuron, where the process is repeated.

We begin at the neuronal membrane. The neuron exists in a fluid environment—it is surrounded by extracellular fluid and contains intracellular fluid (i.e., cytoplasm). The neuronal membrane keeps these two fluids separate—a critical role because the electrical signal that passes through the neuron depends on the intra- and extracellular fluids being electrically different. This difference in charge across the membrane, called the membrane potential , provides energy for the signal.

The electrical charge of the fluids is caused by charged molecules (ions) dissolved in the fluid. The semipermeable nature of the neuronal membrane somewhat restricts the movement of these charged molecules, and, as a result, some of the charged particles tend to become more concentrated either inside or outside the cell.

Between signals, the neuron membrane’s potential is held in a state of readiness, called the resting potential . Like a rubber band stretched out and waiting to spring into action, ions line up on either side of the cell membrane, ready to rush across the membrane when the neuron goes active and the membrane opens its gates (i.e., a sodium-potassium pump that allows movement of ions across the membrane). Ions in high-concentration areas are ready to move to low-concentration areas, and positive ions are ready to move to areas with a negative charge.

In the resting state, sodium (Na + ) is at higher concentrations outside the cell, so it will tend to move into the cell. Potassium (K + ), on the other hand, is more concentrated inside the cell, and will tend to move out of the cell ([link]). In addition, the inside of the cell is slightly negatively charged compared to the outside. This provides an additional force on sodium, causing it to move into the cell.

At resting potential, Na + (blue pentagons) is more highly concentrated outside the cell in the extracellular fluid (shown in blue), whereas K + (purple squares) is more highly concentrated near the membrane in the cytoplasm or intracellular fluid. Other molecules, such as chloride ions (yellow circles) and negatively charged proteins (brown squares), help contribute to a positive net charge in the extracellular fluid and a negative net charge in the intracellular fluid.

From this resting potential state, the neuron receives a signal and its state changes abruptly ([link]). When a neuron receives signals at the dendrites—due to neurotransmitters from an adjacent neuron binding to its receptors—small pores, or gates, open on the neuronal membrane, allowing Na + ions, propelled by both charge and concentration differences, to move into the cell. With this influx of positive ions, the internal charge of the cell becomes more positive. If that charge reaches a certain level, called the threshold of excitation , the neuron becomes active and the action potential begins.

Many additional pores open, causing a massive influx of Na + ions and a huge positive spike in the membrane potential, the peak action potential. At the peak of the spike, the sodium gates close and the potassium gates open. As positively charged potassium ions leave, the cell quickly begins repolarization. At first, it hyperpolarizes, becoming slightly more negative than the resting potential, and then it levels off, returning to the resting potential.

During the action potential, the electrical charge across the membrane changes dramatically.

This positive spike constitutes the action potential : the electrical signal that typically moves from the cell body down the axon to the axon terminals. The electrical signal moves down the axon like a wave at each point, some of the sodium ions that enter the cell diffuse to the next section of the axon, raising the charge past the threshold of excitation and triggering a new influx of sodium ions. The action potential moves all the way down the axon to the terminal buttons.

The action potential is an all-or-none phenomenon. In simple terms, this means that an incoming signal from another neuron is either sufficient or insufficient to reach the threshold of excitation. There is no in-between, and there is no turning off an action potential once it starts. Think of it like sending an email or a text message. You can think about sending it all you want, but the message is not sent until you hit the send button. Furthermore, once you send the message, there is no stopping it.

Because it is all or none, the action potential is recreated, or propagated, at its full strength at every point along the axon. Much like the lit fuse of a firecracker, it does not fade away as it travels down the axon. It is this all-or-none property that explains the fact that your brain perceives an injury to a distant body part like your toe as equally painful as one to your nose.

As noted earlier, when the action potential arrives at the terminal button, the synaptic vesicles release their neurotransmitters into the synapse. The neurotransmitters travel across the synapse and bind to receptors on the dendrites of the adjacent neuron, and the process repeats itself in the new neuron (assuming the signal is sufficiently strong to trigger an action potential). Once the signal is delivered, excess neurotransmitters in the synapse drift away, are broken down into inactive fragments, or are reabsorbed in a process known as reuptake . Reuptake involves the neurotransmitter being pumped back into the neuron that released it, in order to clear the synapse ([link]). Clearing the synapse serves both to provide a clear “on” and “off” state between signals and to regulate the production of neurotransmitter (full synaptic vesicles provide signals that no additional neurotransmitters need to be produced).

Reuptake involves moving a neurotransmitter from the synapse back into the axon terminal from which it was released.

Neuronal communication is often referred to as an electrochemical event. The movement of the action potential down the length of the axon is an electrical event, and movement of the neurotransmitter across the synaptic space represents the chemical portion of the process.

Link to Learning

Click through this interactive simulation for a closer look at neuronal communication.

The Action Potential

The functions of the nervous system—sensation, integration, and response—depend on the functions of the neurons underlying these pathways. To understand how neurons are able to communicate, it is necessary to describe the role of an excitable membrane in generating these signals. The basis of this communication is the action potential, which demonstrates how changes in the membrane can constitute a signal. Looking at the way these signals work in more variable circumstances involves a look at graded potentials, which will be covered in the next section.

Electrically Active Cell Membranes

Most cells in the body make use of charged particles, ions, to build up a charge across the cell membrane. Previously, this was shown to be a part of how muscle cells work. For skeletal muscles to contract, based on excitation–contraction coupling, requires input from a neuron. Both of the cells make use of the cell membrane to regulate ion movement between the extracellular fluid and cytosol.

As you learned in the chapter on cells, the cell membrane is primarily responsible for regulating what can cross the membrane and what stays on only one side. The cell membrane is a phospholipid bilayer, so only substances that can pass directly through the hydrophobic core can diffuse through unaided. Charged particles, which are hydrophilic by definition, cannot pass through the cell membrane without assistance ((Figure)). Transmembrane proteins, specifically channel proteins, make this possible. Several passive transport channels, as well as active transport pumps, are necessary to generate a transmembrane potential and an action potential. Of special interest is the carrier protein referred to as the sodium/potassium pump that moves sodium ions (Na + ) out of a cell and potassium ions (K + ) into a cell, thus regulating ion concentration on both sides of the cell membrane.

The sodium/potassium pump requires energy in the form of adenosine triphosphate (ATP), so it is also referred to as an ATPase. As was explained in the cell chapter, the concentration of Na + is higher outside the cell than inside, and the concentration of K + is higher inside the cell than outside. That means that this pump is moving the ions against the concentration gradients for sodium and potassium, which is why it requires energy. In fact, the pump basically maintains those concentration gradients.

Ion channels are pores that allow specific charged particles to cross the membrane in response to an existing concentration gradient. Proteins are capable of spanning the cell membrane, including its hydrophobic core, and can interact with the charge of ions because of the varied properties of amino acids found within specific domains or regions of the protein channel. Hydrophobic amino acids are found in the domains that are apposed to the hydrocarbon tails of the phospholipids. Hydrophilic amino acids are exposed to the fluid environments of the extracellular fluid and cytosol. Additionally, the ions will interact with the hydrophilic amino acids, which will be selective for the charge of the ion. Channels for cations (positive ions) will have negatively charged side chains in the pore. Channels for anions (negative ions) will have positively charged side chains in the pore. This is called electrochemical exclusion , meaning that the channel pore is charge-specific.

Ion channels can also be specified by the diameter of the pore. The distance between the amino acids will be specific for the diameter of the ion when it dissociates from the water molecules surrounding it. Because of the surrounding water molecules, larger pores are not ideal for smaller ions because the water molecules will interact, by hydrogen bonds, more readily than the amino acid side chains. This is called size exclusion . Some ion channels are selective for charge but not necessarily for size, and thus are called a nonspecific channel . These nonspecific channels allow cations—particularly Na + , K + , and Ca 2+ —to cross the membrane, but exclude anions.

Ion channels do not always freely allow ions to diffuse across the membrane. Some are opened by certain events, meaning the channels are gated . So another way that channels can be categorized is on the basis of how they are gated. Although these classes of ion channels are found primarily in the cells of nervous or muscular tissue, they also can be found in the cells of epithelial and connective tissues.

A ligand-gated channel opens because a signaling molecule, a ligand, binds to the extracellular region of the channel. This type of channel is also known as an ionotropic receptor because when the ligand, known as a neurotransmitter in the nervous system, binds to the protein, ions cross the membrane changing its charge ((Figure)).

A mechanically gated channel opens because of a physical distortion of the cell membrane. Many channels associated with the sense of touch (somatosensation) are mechanically gated. For example, as pressure is applied to the skin, these channels open and allow ions to enter the cell. Similar to this type of channel would be the channel that opens on the basis of temperature changes, as in testing the water in the shower ((Figure)).

A voltage-gated channel is a channel that responds to changes in the electrical properties of the membrane in which it is embedded. Normally, the inner portion of the membrane is at a negative voltage. When that voltage becomes less negative, the channel begins to allow ions to cross the membrane ((Figure)).

A leakage channel is randomly gated, meaning that it opens and closes at random, hence the reference to leaking. There is no actual event that opens the channel instead, it has an intrinsic rate of switching between the open and closed states. Leakage channels contribute to the resting transmembrane voltage of the excitable membrane ((Figure)).

The Membrane Potential

The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential . A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking ((Figure)).

The concentration of ions in extracellular and intracellular fluids is largely balanced, with a net neutral charge. However, a slight difference in charge occurs right at the membrane surface, both internally and externally. It is the difference in this very limited region that has all the power in neurons (and muscle cells) to generate electrical signals, including action potentials.

Before these electrical signals can be described, the resting state of the membrane must be explained. When the cell is at rest, and the ion channels are closed (except for leakage channels which randomly open), ions are distributed across the membrane in a very predictable way. The concentration of Na + outside the cell is 10 times greater than the concentration inside. Also, the concentration of K + inside the cell is greater than outside. The cytosol contains a high concentration of anions, in the form of phosphate ions and negatively charged proteins. Large anions are a component of the inner cell membrane, including specialized phospholipids and proteins associated with the inner leaflet of the membrane (leaflet is a term used for one side of the lipid bilayer membrane). The negative charge is localized in the large anions.

With the ions distributed across the membrane at these concentrations, the difference in charge is measured at -70 mV, the value described as the resting membrane potential . The exact value measured for the resting membrane potential varies between cells, but -70 mV is most commonly used as this value. This voltage would actually be much lower except for the contributions of some important proteins in the membrane. Leakage channels allow Na + to slowly move into the cell or K + to slowly move out, and the Na + /K + pump restores them. This may appear to be a waste of energy, but each has a role in maintaining the membrane potential.

The Action Potential

Resting membrane potential describes the steady state of the cell, which is a dynamic process that is balanced by ion leakage and ion pumping. Without any outside influence, it will not change. To get an electrical signal started, the membrane potential has to change.

This starts with a channel opening for Na + in the membrane. Because the concentration of Na + is higher outside the cell than inside the cell by a factor of 10, ions will rush into the cell that are driven largely by the concentration gradient. Because sodium is a positively charged ion, it will change the relative voltage immediately inside the cell relative to immediately outside. The resting potential is the state of the membrane at a voltage of -70 mV, so the sodium cation entering the cell will cause it to become less negative. This is known as depolarization , meaning the membrane potential moves toward zero.

The concentration gradient for Na + is so strong that it will continue to enter the cell even after the membrane potential has become zero, so that the voltage immediately around the pore begins to become positive. The electrical gradient also plays a role, as negative proteins below the membrane attract the sodium ion. The membrane potential will reach +30 mV by the time sodium has entered the cell.

As the membrane potential reaches +30 mV, other voltage-gated channels are opening in the membrane. These channels are specific for the potassium ion. A concentration gradient acts on K + , as well. As K + starts to leave the cell, taking a positive charge with it, the membrane potential begins to move back toward its resting voltage. This is called repolarization , meaning that the membrane voltage moves back toward the -70 mV value of the resting membrane potential.

Repolarization returns the membrane potential to the -70 mV value that indicates the resting potential, but it actually overshoots that value. Potassium ions reach equilibrium when the membrane voltage is below -70 mV, so a period of hyperpolarization occurs while the K + channels are open. Those K + channels are slightly delayed in closing, accounting for this short overshoot.

What has been described here is the action potential, which is presented as a graph of voltage over time in (Figure). It is the electrical signal that nervous tissue generates for communication. The change in the membrane voltage from -70 mV at rest to +30 mV at the end of depolarization is a 100-mV change. That can also be written as a 0.1-V change. To put that value in perspective, think about a battery. An AA battery that you might find in a television remote has a voltage of 1.5 V, or a 9-V battery (the rectangular battery with two posts on one end) is, obviously, 9 V. The change seen in the action potential is one or two orders of magnitude less than the charge in these batteries. In fact, the membrane potential can be described as a battery. A charge is stored across the membrane that can be released under the correct conditions. A battery in your remote has stored a charge that is “released” when you push a button.

What happens across the membrane of an electrically active cell is a dynamic process that is hard to visualize with static images or through text descriptions. View this animation to learn more about this process. What is the difference between the driving force for Na + and K + ? And what is similar about the movement of these two ions?

The question is, now, what initiates the action potential? The description above conveniently glosses over that point. But it is vital to understanding what is happening. The membrane potential will stay at the resting voltage until something changes. The description above just says that a Na + channel opens. Now, to say “a channel opens” does not mean that one individual transmembrane protein changes. Instead, it means that one kind of channel opens. There are a few different types of channels that allow Na + to cross the membrane. A ligand-gated Na + channel will open when a neurotransmitter binds to it and a mechanically gated Na + channel will open when a physical stimulus affects a sensory receptor (like pressure applied to the skin compresses a touch receptor). Whether it is a neurotransmitter binding to its receptor protein or a sensory stimulus activating a sensory receptor cell, some stimulus gets the process started. Sodium starts to enter the cell and the membrane becomes less negative.

A third type of channel that is an important part of depolarization in the action potential is the voltage-gated Na + channel. The channels that start depolarizing the membrane because of a stimulus help the cell to depolarize from -70 mV to -55 mV. Once the membrane reaches that voltage, the voltage-gated Na + channels open. This is what is known as the threshold. Any depolarization that does not change the membrane potential to -55 mV or higher will not reach threshold and thus will not result in an action potential. Also, any stimulus that depolarizes the membrane to -55 mV or beyond will cause a large number of channels to open and an action potential will be initiated.

Because of the threshold, the action potential can be likened to a digital event—it either happens or it does not. If the threshold is not reached, then no action potential occurs. If depolarization reaches -55 mV, then the action potential continues and runs all the way to +30 mV, at which K + causes repolarization, including the hyperpolarizing overshoot. Also, those changes are the same for every action potential, which means that once the threshold is reached, the exact same thing happens. A stronger stimulus, which might depolarize the membrane well past threshold, will not make a “bigger” action potential. Action potentials are “all or none.” Either the membrane reaches the threshold and everything occurs as described above, or the membrane does not reach the threshold and nothing else happens. All action potentials peak at the same voltage (+30 mV), so one action potential is not bigger than another. Stronger stimuli will initiate multiple action potentials more quickly, but the individual signals are not bigger. Thus, for example, you will not feel a greater sensation of pain, or have a stronger muscle contraction, because of the size of the action potential because they are not different sizes.

As we have seen, the depolarization and repolarization of an action potential are dependent on two types of channels (the voltage-gated Na + channel and the voltage-gated K + channel). The voltage-gated Na + channel actually has two gates. One is the activation gate , which opens when the membrane potential crosses -55 mV. The other gate is the inactivation gate , which closes after a specific period of time—on the order of a fraction of a millisecond. When a cell is at rest, the activation gate is closed and the inactivation gate is open. However, when the threshold is reached, the activation gate opens, allowing Na + to rush into the cell. Timed with the peak of depolarization, the inactivation gate closes. During repolarization, no more sodium can enter the cell. When the membrane potential passes -55 mV again, the activation gate closes. After that, the inactivation gate re-opens, making the channel ready to start the whole process over again.

The voltage-gated K + channel has only one gate, which is sensitive to a membrane voltage of -50 mV. However, it does not open as quickly as the voltage-gated Na + channel does. It might take a fraction of a millisecond for the channel to open once that voltage has been reached. The timing of this coincides exactly with when the Na + flow peaks, so voltage-gated K + channels open just as the voltage-gated Na + channels are being inactivated. As the membrane potential repolarizes and the voltage passes -50 mV again, the channel closes—again, with a little delay. Potassium continues to leave the cell for a short while and the membrane potential becomes more negative, resulting in the hyperpolarizing overshoot. Then the channel closes again and the membrane can return to the resting potential because of the ongoing activity of the non-gated channels and the Na + /K + pump.

All of this takes place within approximately 2 milliseconds ((Figure)). While an action potential is in progress, another one cannot be initiated. That effect is referred to as the refractory period . There are two phases of the refractory period: the absolute refractory period and the relative refractory period . During the absolute phase, another action potential will not start. This is because of the inactivation gate of the voltage-gated Na + channel. Once that channel is back to its resting conformation (less than -55 mV), a new action potential could be started, but only by a stronger stimulus than the one that initiated the current action potential. This is because of the flow of K + out of the cell. Because that ion is rushing out, any Na + that tries to enter will not depolarize the cell, but will only keep the cell from hyperpolarizing.

Propagation of the Action Potential

The action potential is initiated at the beginning of the axon, at what is called the initial segment. There is a high density of voltage-gated Na + channels so that rapid depolarization can take place here. Going down the length of the axon, the action potential is propagated because more voltage-gated Na + channels are opened as the depolarization spreads. This spreading occurs because Na + enters through the channel and moves along the inside of the cell membrane. As the Na + moves, or flows, a short distance along the cell membrane, its positive charge depolarizes a little more of the cell membrane. As that depolarization spreads, new voltage-gated Na + channels open and more ions rush into the cell, spreading the depolarization a little farther.

Because voltage-gated Na + channels are inactivated at the peak of the depolarization, they cannot be opened again for a brief time—the absolute refractory period. Because of this, depolarization spreading back toward previously opened channels has no effect. The action potential must propagate toward the axon terminals as a result, the polarity of the neuron is maintained, as mentioned above.

Propagation, as described above, applies to unmyelinated axons. When myelination is present, the action potential propagates differently. Sodium ions that enter the cell at the initial segment start to spread along the length of the axon segment, but there are no voltage-gated Na + channels until the first node of Ranvier. Because there is not constant opening of these channels along the axon segment, the depolarization spreads at an optimal speed. The distance between nodes is the optimal distance to keep the membrane still depolarized above threshold at the next node. As Na + spreads along the inside of the membrane of the axon segment, the charge starts to dissipate. If the node were any farther down the axon, that depolarization would have fallen off too much for voltage-gated Na + channels to be activated at the next node of Ranvier. If the nodes were any closer together, the speed of propagation would be slower.

Propagation along an unmyelinated axon is referred to as continuous conduction along the length of a myelinated axon, it is saltatory conduction . Continuous conduction is slow because there are always voltage-gated Na + channels opening, and more and more Na + is rushing into the cell. Saltatory conduction is faster because the action potential basically jumps from one node to the next (saltare = “to leap”), and the new influx of Na + renews the depolarized membrane. Along with the myelination of the axon, the diameter of the axon can influence the speed of conduction. Much as water runs faster in a wide river than in a narrow creek, Na + -based depolarization spreads faster down a wide axon than down a narrow one. This concept is known as resistance and is generally true for electrical wires or plumbing, just as it is true for axons, although the specific conditions are different at the scales of electrons or ions versus water in a river.

Potassium Concentration Glial cells, especially astrocytes, are responsible for maintaining the chemical environment of the CNS tissue. The concentrations of ions in the extracellular fluid are the basis for how the membrane potential is established and changes in electrochemical signaling. If the balance of ions is upset, drastic outcomes are possible.

Normally the concentration of K + is higher inside the neuron than outside. After the repolarizing phase of the action potential, K + leakage channels and the Na + /K + pump ensure that the ions return to their original locations. Following a stroke or other ischemic event, extracellular K + levels are elevated. The astrocytes in the area are equipped to clear excess K + to aid the pump. But when the level is far out of balance, the effects can be irreversible.

Astrocytes can become reactive in cases such as these, which impairs their ability to maintain the local chemical environment. The glial cells enlarge and their processes swell. They lose their K + buffering ability and the function of the pump is affected, or even reversed. One of the early signs of cell disease is this “leaking” of sodium ions into the body cells. This sodium/potassium imbalance negatively affects the internal chemistry of cells, preventing them from functioning normally.

Visit this site to see a virtual neurophysiology lab, and to observe electrophysiological processes in the nervous system, where scientists directly measure the electrical signals produced by neurons. Often, the action potentials occur so rapidly that watching a screen to see them occur is not helpful. A speaker is powered by the signals recorded from a neuron and it “pops” each time the neuron fires an action potential. These action potentials are firing so fast that it sounds like static on the radio. Electrophysiologists can recognize the patterns within that static to understand what is happening. Why is the leech model used for measuring the electrical activity of neurons instead of using humans?

Chapter Review

The nervous system is characterized by electrical signals that are sent from one area to another. Whether those areas are close or very far apart, the signal must travel along an axon. The basis of the electrical signal is the controlled distribution of ions across the membrane. Transmembrane ion channels regulate when ions can move in or out of the cell, so that a precise signal is generated. This signal is the action potential which has a very characteristic shape based on voltage changes across the membrane in a given time period.

The membrane is normally at rest with established Na + and K + concentrations on either side. A stimulus will start the depolarization of the membrane, and voltage-gated channels will result in further depolarization followed by repolarization of the membrane. A slight overshoot of hyperpolarization marks the end of the action potential. While an action potential is in progress, another cannot be generated under the same conditions. While the voltage-gated Na + channel is inactivated, absolutely no action potentials can be generated. Once that channel has returned to its resting state, a new action potential is possible, but it must be started by a relatively stronger stimulus to overcome the K + leaving the cell.

The action potential travels down the axon as voltage-gated ion channels are opened by the spreading depolarization. In unmyelinated axons, this happens in a continuous fashion because there are voltage-gated channels throughout the membrane. In myelinated axons, propagation is described as saltatory because voltage-gated channels are only found at the nodes of Ranvier and the electrical events seem to “jump” from one node to the next. Saltatory conduction is faster than continuous conduction, meaning that myelinated axons propagate their signals faster. The diameter of the axon also makes a difference as ions diffusing within the cell have less resistance in a wider space.

Interactive Link Questions

What happens across the membrane of an electrically active cell is a dynamic process that is hard to visualize with static images or through text descriptions. View this animation to really understand the process. What is the difference between the driving force for Na + and K + ? And what is similar about the movement of these two ions?

Sodium is moving into the cell because of the immense concentration gradient, whereas potassium is moving out because of the depolarization that sodium causes. However, they both move down their respective gradients, toward equilibrium.

Visit this site to see a virtual neurophysiology lab, and to observe electrophysiological processes in the nervous system, where scientists directly measure the electrical signals produced by neurons. Often, the action potentials occur so rapidly that watching a screen to see them occur is not helpful. A speaker is powered by the signals recorded from a neuron and it “pops” each time the neuron fires an action potential. These action potentials are firing so fast that it sounds like static on the radio. Electrophysiologists can recognize the patterns within that static to understand what is happening. Why is the leech model used for measuring the electrical activity of neurons instead of using humans?

The properties of electrophysiology are common to all animals, so using the leech is an easier, more humane approach to studying the properties of these cells. There are differences between the nervous systems of invertebrates (such as a leech) and vertebrates, but not for the sake of what these experiments study.

What Is the Function of the Axon Terminal?

The axon terminal holds a very important function in the brain and is a key part of nervous system function. An axon is a process that extends out from a brain cell. These processes can either be dendrites or axons. The terminal of the axon, generally speaking, allows the axon to make connections to other brain cells, in which neurotransmitters, such as dopamine or serotonin, flow through.

What Are the Parts of a Neuron?

A neuron is the more scientific term for a brain cell, and it has a specific structure. Its body is called the soma, and the processes that extend from it are either dendrites or axons, which both have different functionality. Dendrites have more to do with the storage and processing of information that neurotransmitter movement. However, dendrites can receive an excitatory or inhibitory signal or both. An excitatory signal fires the dendrite, which creates a message, known as action potential, which travels down the axon. Inhibitory signals prevent firing. These axons receive messages and send them through their terminals at the synapse, which is a complete neuron-to-neuron connection.

Who Are the Functions of a Neuron?

T he three basic functions of a neuron are to discern whether signals should be passed to other neurons to receive signals from other neurons and to communicate signals to other cells, which can be neurons or other cells. The axon and its terminal are at the heart of the messaging system.

What Is the Axon and Axon Terminal Responsible For?

T he axon and its terminal are at the heart of the messaging centers in the brain. After a message travels down the axon to the terminal, a connection is made with the synapse. These small connections in these

gaps (synapses) allow the terminal to pass information along to another cell, often triggering the release of a neurotransmitter. Based on the type of message sent, this message center can also prevent a message from being passed.

What Are Neurotransmitters?

A neurotransmitter is essentially a messenger in the brain. After the neuron-to-neuron connection is made, the message must then be sent, and different neurotransmitters relay different messages. Neurotransmitters can be responsible for regulating heart rate, helping with mood and concentration, aiding in digestion, or controlling muscle movement. There are three types of neurotransmitters, which compare to the messages sent in the brain. These are excitatory neurotransmitters, which implore action, inhibitory neurotransmitters, which likely prevent action, and modulatory neurotransmitters, which are communicators and can be either excitatory or inhibitory, depending on the situation.

What Are Common Names of Neurotransmitters?

N eurotransmitters that students or patients may be familiar with include:

  • A cetylcholine
  • : Regulates muscle control, but is also related to memory and cognition
  • Dopamine : Which is related to mood, memory, and cognition but also muscle movement
  • Endorphins : Which are pain inhibitors and can create euphoria
  • Epinephrine : Which is another term for adrenaline, which is the body’s fight-or-flight mechanism
  • Gamma-aminobutyric acid (GABA) : Which regulates mood
  • Serotonin , which is related to mood, sleep, appetite, and Circadian rhythm

I n addition to these, there are more than 100 neurotransmitters present in the brain at any given time.

What Happens When There Is a Brain Imbalance?

R egardless of how well the axon and its terminal are doing their jobs, there can sometimes be imbalances of neurotransmitters in the brain, which are often linked with psychological or physical disorders. These can be milder, such as seasonal affective disorder (SAD), which is directly connected to lower levels of serotonin, or they can be more severe, as a lack of dopamine is connected to the neurological disorder Parkinson’s disease. Too much GABA in the brain is linked to anxiety, while high levels of acetylcholine are linked to epilepsy and seizures. Medications are the first-line treatment when it comes to neurotransmitter imbalances in the brain.

Chapter 8 Summary

In this chapter, you learned about the human nervous system. Specifically, you learned that:

  • The nervous system is the organ system that coordinates all of the body’s voluntary and involuntary actions by transmitting signals to and from different parts of the body. It has two major divisions: the central nervous system (CNS) and the peripheral nervous system (PNS).
    • The CNS includes the brain and spinal cord.
    • The PNS consists mainly of nerves that connect the CNS with the rest of the body. It has two major divisions: the somatic nervous system and the autonomic nervous system . These divisions control different types of functions, and often interact with the CNS to carry out these functions. The somatic system controls activities that are under voluntary control. The autonomic system controls activities that are involuntary.
      • The autonomic nervous system is further divided into the sympathetic division (which controls the fight-or-flight response), the parasympathetic division (which controls most routine involuntary responses), and the enteric division (which provides local control for digestive processes).
      • Signals sent by the nervous system are electrical signals called nerve impulses . They are transmitted by special, electrically excitable cells called neurons , which are one of two major types of cells in the nervous system.
      • Neuroglia are the other major type of nervous system cells. There are many types of glial cells, and they have many specific functions. In general, neuroglia function to support, protect, and nourish neurons.
      • The main parts of a neuron include the cell body , dendrites , and axon . The cell body contains the nucleus. Dendrites receive nerve impulses from other cells, and the axon transmits nerve impulses to other cells at axon terminals. A synapse is a complex membrane junction at the end of an axon terminal that transmits signals to another cell.
      • Axons are often wrapped in an electrically-insulating myelin sheath , which is produced by oligodendrocytes or schwann cells, both of which are types of neuroglia. Electrical impulses called action potentials occur at gaps in the myelin sheath, called nodes of Ranvier , which speeds the conduction of nerve impulses down the axon.
      • Neurogenesis , or the formation of new neurons by cell division, may occur in a mature human brain — but only to a limited extent.
      • The nervous tissue in the brain and spinal cord consists of gray matter — which contains mainly unmyelinated cell bodies and dendrites of neurons — and white matter, which contains mainly myelinated axons of neurons. Nerves of the peripheral nervous system consist of long bundles of myelinated axons that extend throughout the body.
      • There are hundreds of types of neurons in the human nervous system, but many can be classified on the basis of the direction in which they carry nerve impulses. Sensory neurons carry nerve impulses away from the body and toward the central nervous system, motor neurons carry them away from the central nervous system and toward the body, and interneurons often carry them between sensory and motor neurons.
      • A nerve impulse is an electrical phenomenon that occurs because of a difference in electrical charge across the plasma membrane of a neuron.
      • The sodium-potassium pump maintains an electrical gradient across the plasma membrane of a neuron when it is not actively transmitting a nerve impulse. This gradient is called the resting potential of the neuron.
      • An action potential is a sudden reversal of the electrical gradient across the plasma membrane of a resting neuron. It begins when the neuron receives a chemical signal from another cell or some other type of stimulus. The action potential travels rapidly down the neuron’s axon as an electric current.
      • A nerve impulse is transmitted to another cell at either an electrical or a chemical synapse . At a chemical synapse, neurotransmitter chemicals are released from the presynaptic cell into the synaptic cleft between cells. The chemicals travel across the cleft to the postsynaptic cell and bind to receptors embedded in its membrane.
      • There are many different types of neurotransmitters. Their effects on the postsynaptic cell generally depend on the type of receptor they bind to. The effects may be excitatory, inhibitory, or modulatory in more complex ways. Both physical and mental disorders may occur if there are problems with neurotransmitters or their receptors.
      • The CNS includes the brain and spinal cord. It is physically protected by bones , meninges , and cerebrospinal fluid . It is chemically protected by the blood-brain barrier.
      • The brain is the control center of the nervous system and of the entire organism. The brain uses a relatively large proportion of the body’s energy, primarily in the form of glucose .
        • The brain is divided into three major parts, each with different functions: the forebrain, the midbrain and the hindbrain.
          • The forebrain includes the cerebrum , the thalamus , the hypothalamus , the hippocampus and the amygdala . The cerebrum is further divided into left and right hemispheres. Each hemisphere has four lobes: frontal, parietal, temporal, and occipital. Each lobe is associated with specific senses or other functions. The cerebrum has a thin outer layer called the cerebral cortex. Its many folds give it a large surface area. This is where most information processing takes place.
          • A spinal cord injury may lead to paralysis (loss of sensation and movement) of the body below the level of the injury, because nerve impulses can no longer travel up and down the spinal cord beyond that point.
          • The PNS is not as well protected physically or chemically as the CNS, so it is more prone to injury and disease. PNS problems include injury from diabetes, shingles, and heavy metal poisoning. Two disorders of the PNS are Guillain-Barre syndrome and Charcot-Marie-Tooth disease.
          • Touch includes the ability to sense pressure, vibration, temperature, pain, and other tactile stimuli. The skin includes several different types of touch receptor cells.
          • Vision is the ability to sense light and see. The eye is the special sensory organ that collects and focuses light, forms images, and changes them to nerve impulses. Optic nerves send information from the eyes to the brain, which processes the visual information and “tells” us what we are seeing.
            • Common vision problems include myopia (nearsightedness), hyperopia (farsightedness), and presbyopia (age-related decline in close vision).

            In addition to the nervous system, there is another system of the body that is important for coordinating and regulating many different functions – the endocrine system. You will learn about the endocrine system in the next chapter.

            Sending Signals: The Nervous System

            The nervous system is the major system of communication within the body. Our thoughts, emotions, and actions are all left up to the signalling done by this system. In tandem with the endocrine system, the nervous system helps regulate and control internal conditions to maintain homeostasis. Most all of the glands discussed in the endocrine system are signaled by nerves to secrete their hormones. However, the nervous system also responds to external stimuli like light and temperature. Every response our body has to any stimulus, whether internal or external, is controlled by the nervous system.

            The nervous system allows you to communicate, show emotion, and interact with others.

            Divisions of the Nervous System

            The nervous system has several divisions, all branching from the central nervous system (CNS). The CNS houses the brain and spinal cord that act as the central command for all actions of the body. Nerves in the brain and nerves that extend from the spinal cord to the various regions of the body create the peripheral nervous system (PNS). The PNS is responsible for linking the body to the CNS so that signals created by the CNS are able to reach their targets. Within the PNS are the somatic nervous system and the autonomic nervous system. The somatic nervous system controls voluntary body movements, like muscular contractions, and the autonomic nervous system controls involuntary movements, like the dilation of your pupils or rhythm of your heartbeat. Finally, within the autonomic nervous system are the sympathetic (SNS) and parasympathetic (PSNS) systems. The SNS preps the body for action, creating the flight or fight response to stimuli. In contrast, the PSNS relaxes the body, bringing it back to normal after an exciting stimulus.

            Structure of a Neuron

            Despite how intricate this system may seem, nervous tissue comes from just two types of cells: glial cells and neurons. Glial cells, also known as neuroglia, are found in both the CNS and PNS. These cells protect and support nerve cells called neurons. Neurons are the basic functional unit of the nervous system, transmitting messages around the body. Their unique structure allows them to be very fast, efficient communicators. Neurons have a cell body that holds a nucleus, which acts as the “brain” of the cell. Surrounding the cell body are dendrites, the regions that receive signals. Dendrites send the signal through the axon until it reaches the axon terminals. The signal travels through the axon with the help of Schwann cells that wrap around the axon and act as an insulator. Between these cells are nodes of Ranvier. A typical neuron is shown in this diagram:

            Just like you send a text to a friend, your neurons send messages to one another.

            Sending a Signal

            The process of sending a signal begins with a stimulus. The dendrites of the first neuron in the signal chain receives the stimulus and transmit the signal through the axon. Once through the axon the signal travels down each axon terminal. When the signal reaches the terminal it causes the release of synaptic vesicles that carry a neurotransmitter (chemical messengers). The vesicle fuses with the membrane of the axon terminal, releasing the neurotransmitter into the synaptic cleft, or synapse. The neurotransmitter then travels across the synapse until it reaches another neuron’s dendrites or the target cell/tissue. For example, the mechanism of signaling muscular contraction begins when the neuron that is part of the motor unit releases a neurotransmitter called acetylcholine (Ach) into the synaptic cleft. Ach travels across the cleft until it reaches the Ach receptors in the membrane of the muscle fiber. Once there, channels open to allow an influx of charged particles that signal the release of calcium, starting the contraction process. A diagram of a typical neuromuscular junction is shown below:

            The Autonomic Nervous System

            As mentioned above, the autonomic nervous system is divided into the parasympathetic and sympathetic systems. A key role of the PSNS is stimulating saliva production in the mouth and stimulating the stomach and intestines to complete digestion. The PSNS maintains a calm state of arousal, with its function often simplified to “rest and digest”. Conversely, the SNS creates alertness in the body. When you are scared, you may notice an increased heart rate, faster breathing, and an energized feeling. This is due to the SNS readying your body to face a potential threat. When the threat is gone, the PSNS will return the body to its normal, calmer state. The diagram below details the effects of the PSNS and SNS on the body and also distinguishes the CNS and PNS from one another:

            Anatomy and Physiology: The Neuromuscular Junction

            A myofiber is an extraordinarily sophisticated piece of cellular machinery, but, in the end, it still only does what it is told! Each muscle cell that contracts is connected to a motor neuron. Muscles, when they contract, go whole hog, which means each cell is in an all-or-nothing mode. In order for a large muscle to have a strong contraction means that every cell in that muscle must be told to contract weaker contractions mean fewer cells contract. So how does a nerve cell tell a muscle cell to contract?

            First, the nerve and muscle cells must make contact, yet the two cells don't actually touch. The junction between a neuron and a muscle fiber is called the neuromuscular junction (NMJ) (see Figure 8.3). The junction, just as in the junction between neurons, is called a chemical synapse, and there is always a space between the cells called a synaptic cleft.

            Figure 8.3 The parts of a neuromuscular junction. (Michael J. Vieira Lazaroff)

            The membranes of the two cells in a synapse are named because of the direction of the nerve impulse: the presynaptic membrane (the neurolemma) and the postsynaptic membrane (the sarcolemma). The message transmitted from the neuron to the myofiber is a chemical one called a neurotransmitter, and they work by changing the permeability of the postsynaptic membrane. This type of synapse, with a synaptic cleft, is a chemical synapse heart cells, and many nerve cells, have electrical synapses, in which the cells actually touch and travel through communicating junctions called gap junctions.

            Neurotransmitters and Exocytosis

            Neurotransmitters are chemical messengers that travel across the synaptic cleft between neurons and neurons, or neurons and myofibers. A neurotransmitter called acetylcholine (ACh) is used at the neuromuscular junction. Acetylcholine is initially produced in the Golgi bodies (in the cell body), and then travels down the axon to the axon terminal bud in synaptic vesicles since there is no E.R., and no Golgi bodies, in the terminal bud, the synaptic vesicles are recycled using both endocytosis, exocytosis, and mitochondria to recycle the ACh.

            So what does it mean to change ?the permeability of the postsynaptic membrane?? To start off, have another look again at active transport. You might remember that active transport is the movement of molecules against the concentration gradient, from a low concentration to a high concentration. In this case, using a nifty little engine called the Na + /K + pump, sodium ions are kept at a high concentration in the synaptic cleft. The sarcolemma, when in this state, is considered polarized. Now remember, keeping up this membrane polarized takes energy, in the form of ATP. Ironically, this energy is used to keep the muscle relaxed.

            At this point it is a good idea to look at what the word relaxed actually means. Most people envision relaxed as being somewhat akin to a teenager crashed on a couch, but that is nothing like relaxed muscle. Survival depends on the ability to react quickly in emergency situations, and a quick mobilization of muscles is crucial to that ability. In that sense, a relaxed muscle is a lot like a bow and arrow, with the arrow pulled back ready to be released. The bow and arrow, even though they are not moving, are primed to move quickly just like a muscle, this state also requires energy.

            The big advantage to active transport, in this situation, is that it creates a situation in which the sarcolemma can become depolarized all the more quickly. Diffusion alone is not the fastest way to move the sodium back to a state of equilibrium. The fastest way, without a doubt, is through facilitated diffusion. Facilitated diffusion requires a channel for the sodium to pass through, but if the channel were always open it would be awfully hard to maintain active transport. There has to be a way to open and close the channel when needed. When the muscle is relaxed, the channel is closed it is only opened when the muscle cell needs to contract. It makes sense that such a channel should be kept under lock and key. The neurotransmitter is the chemical message that tells the cell to contract the neurotransmitter, a cool molecule called acetylcholine (ACh), is the key. The ACh is kept in synaptic vesicles in the axon terminal bud. When the axon receives the message, via a similar change in the polarization of the neurilemma, the synaptic vesicle fuses with the neurilemma and releases its contents (the ACh) into the synaptic cleft through exocytosis. The key has been released all the key needs now is a lock.

            ACh, Receptors, and Facilitated Diffusion

            All along the postsynaptic membrane, the sarcolemma, are receptors for the acetylcholine (ACh). The ACh binds with the ACh receptors, which open the channel, allowing the sodium ions to flood through the postsynaptic membrane via facilitated diffusion. Once again, the combination of active transport and facilitated diffusion makes this and depolarization incredibly fast (only two milliseconds!).

            The only problem with this scenario is how the muscle gets relaxed again. This is easier to understand when you think about the enzyme acetylcholinesterase (ACh-esterase). When the ACh is released into the synaptic cleft, it is broken down very quickly by the acetylcholinesterase. In order to maintain a sustained contraction, the motor neuron needs to release an almost continuous supply of ACh?luckily there's a constant recycling of the neurotransmitter, or it would not be possible to contract a muscle for more than a few milliseconds!

            My, Oh, Myogram!

            Have you ever heard of a muscle twitch? A myogram is a graphic representation of the speed and strength of a muscle contraction (see Figure 8.4). To understand a myogram, let's start by looking at a muscle twitch. In this graph, the X-axis indicates time, and the Y-axis indicates the strength of the muscle contraction. If you look at the following figure, you will notice that a flat line indicates the relaxed muscle, and that the quick contraction and relaxation are indicated by the bell curve.

            What you may not notice right away is the location of the stimulus by the motor neuron. If you look carefully you'll notice that the contraction does not start right after the stimulus, but that there is a delay called the latent period, before the muscle contraction actually starts. What is happening here, during the latent period? Think about it, for there are several steps, in order: exocytosis of the ACh, ACh binds to the ACh receptors, the channels open, and Na + ions flood through the newly opened channels (facilitated diffusion).

            The rise of the curve is called the contraction period, and the decline is called the relaxation period. The relaxation period, however, is a reversal of the latent period: The ACh is broken down by the acetylcholinesterase, the ACh receptor channels close, and active transport returns the Na + ions to the synaptic cleft. So why is this period so much longer than the latent period? Remember, since active transport has to move the ions upstream, it does take longer, but also remember that facilitated diffusion is so much faster when it is preceded by active transport!

            Excerpted from The Complete Idiot's Guide to Anatomy and Physiology 2004 by Michael J. Vieira Lazaroff. All rights reserved including the right of reproduction in whole or in part in any form. Used by arrangement with Alpha Books, a member of Penguin Group (USA) Inc.


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            Our Electric Mind: The Neuron Doctrine

            The Neuron Doctrine established that neurons are the individual cellular units of the nervous system, surrounded by a cellular membrane and separate from other structures like the cells in any other organ in the body. Unlike most cells in the body, however, neurons are specifically designed to receive and to transmit information.

            Santiago Ramon y Cajal, the Spanish neuroscientist (Image: By Original photo is anonymous although published by Clark University in 1899/Public Domain)

            This Neuron Doctrine was championed by the most famous neuroanatomist who has ever lived, Santiago Ramon y Cajal. The winner of the 1906 Nobel Prize, Cajal determined that in young animals you could actually follow axons with that specific method to their termination. From these studies he established that neurons were structural and functional units.

            That neurons are the individual units of the nervous system and separate from other cells was also suggested by Sir Charles Sherrington—who also won a Nobel Prize. Sherrington, on the basis of theoretic considerations alone, believed that neurons had to have a space in between them, a gap in between the various neurons in the nervous system. When he looked at conduction as a physiologist—looked at conduction in nerve trunks—it was much faster than if he looked in gray matter in the brain. On the basis of that alone, he believed that neurons were individual structural units that had to have a space or a gap in between them. This was all the more important since synapses were not actually seen with an electron microscope until the early 1950s.

            This is a transcript from the video series Understanding the Brain. Watch it now, Wondrium.

            We believe that synapses are the places in the brain where one neuron interacts with another neuron. A synapse is where the communication takes place between one neuron and the next neuron in the chain. The axon terminal is where the first neuron makes contact with the second. At the terminal, there are synaptic vesicles, which release a chemical that will interact with the postsynaptic membrane—the dendrites or the cell body of that second neuron.

            Bridging the Gap between Neurons

            How do neurons communicate with each other? If there is a gap between them, what is responsible for the communication? A great advance forward in understanding this came about with the discovery that axons actually generate electricity.

            Anatomy of a neuron (Image: By ShadeDesign/Shutterstock)

            An electrical signal gets propagated and it begins at the axon hillock. One of the most important things to remember is that the axon is not just an extension of the cell body, it’s a specialized structure and it’s attached to the cell body at the axon hillock. An electrical signal is generated at the axon hillock and it’s propagated down the axon, in an “all-or-none” fashion. That means that the signal does not degrade. The signal will travel down the axon in a particular way. It jumps from node to node, in between the myelin wrappings.

            If all action potentials of a given neuron are the same amplitude and they don’t degrade, then how is it that intensity would be encoded in the nervous system or encoded in a neuron like this? And what is responsible for the quality of the stimulation? We need to learn something about what the code is.

            The Intensity and Quality of a Stimulus

            The intensity of a stimulus is encoded in neurons by changing the frequency of the firing. A more intense stimulus causes neurons to increase their firing rate. The quality of the stimulus, on the other hand, is a little bit different. The quality of a stimulus is the result of the stimulation of different kinds of neurons, transmission along specific pathways, and also “interpretation” by different areas of the brain, especially the cerebral cortex.

            Let’s think about this in terms of vision. The quality of the stimulus in vision—what we experience ultimately as vision—comes about because an electrical signal is started by cells in the eye that absorb light. These cells have to be specialized to absorb light. Then an electrical signal is transmitted to the brain along visual pathways. That’s what it means to say that the brain is made up of these various types of systems. Ultimately, the interpretation—or what mental construct we interpret as seeing—is the result of these pathways eventually reaching the cortex and being interpreted by very specific visual areas of the brain. The neurons themselves are going to communicate always with these potentials that are generated in axons.

            What is actually happening when this action potential or this electrical signal is being generated in an axon? To appreciate this and how neurons communicate, we have to understand something about the internal and the external environment of neurons and how the change in the distribution of particular atoms is going to be the signaling mechanism for transmitting information.

            Neurons are structural and functional units of the nervous system. They are cells like any other cell of the body.

            Neurons are structural and functional units of the nervous system. They are cells like any other cell of the body. They have a membrane surrounding them that makes them a separate unit. This is inside the cell. And neurons, like almost all cells in the body, have organelles inside of them. They have special structures that are involved in making proteins, for example, packaging proteins. They also have within them atoms that are ions, which are basically charged atoms, and that just means atoms that have either gained or lost an electron.

            Charging the Neuron

            Inside of the cell body, there are organelles and ions and other molecules. Outside of the neuronal cell membrane is extracellular space. In this extracellular space there are also ions. You could find potassium again, sodium, chloride, calcium, other ions. What is important in understanding how signaling takes place in the nervous system is to realize that the distribution of ions in a cell, in a neuron, is different between the inside and the outside of the cell. The ions are distributed unequally across the neuronal membrane, so that in what we refer to as the resting state, the inside of the cell is going to be more negatively charged than the outside. That is a fundamental principle. The resting state means the neuron at a time when it is not firing. In its resting state the ions are distributed unequally across the membrane so that the inside of this cell is more negative than the outside.

            This charge differential—because remember, ions are basically atoms that have either gained or lost an electron, so they are charged—is maintained in a number of ways. One of the ways it’s maintained is that in the membrane of neurons are molecules that act as little pumps, and they make sure that the intracellular ion concentration is regulated very carefully. It’s very important that the ionic concentrations be regulated, because any abnormality in this system or control mechanisms can lead to an abnormal electrical discharge. And an abnormal electrical discharge could set up seizures in the brain or could even kill neurons. In the resting state, this charge differential is maintained by molecules that actually exist in the membrane, that act as little pumps that make sure the right charged ions are distributed across the membrane in a very particular way.

            Regulating Ionic Concentration

            In the extracellular space, which is outside of a single neuron, the role of regulating ion concentration is the job of astrocytes. Astrocytes—star-shaped glial cells derived from the same progenitor cells that give rise to neurons—play a critical role in regulating the ionic concentration outside of the neuron. They do this because they actually act as little sinks for particular charged atoms. The extracellular ionic environment is regulated down to the atom by astrocytes and the intracellular charge is going to be regulated down to the atom by specific molecules across the membrane.

            What happens when a neuron is stimulated? When a neuron is stimulated, the distribution of ions is altered across the membrane. If ions now become distributed when the cell is stimulated, the differential charge results in the inside of the neuron becoming more positive we call that depolarization. If the inside of the cell becomes even more negative than it was before, then it’s going to become hyperpolarized. In the resting state the charge differential is about -70 mV.

            How to Fire a Neuron

            When the charge reaches a particular point—when the inside of the cell becomes more positive to about -55 mV—it sets off an action potential at the axon hillock. What we have then is depolarization—making the inside more positive—an excitation in the nervous system. If the inside is more negative, it’s called hyperpolarization—an inhibition in the nervous system. Action potentials are generated at that axon hillock of the neuron and propagated down the axon, jumping from node to node in between the myelin sheaths (see fig 1). Their very rapid and transient changes in the membrane potential are going to occur at every place where the axon is basically bare. Because the action potential jumps from node to node, it’s called saltatory conduction. That means a “jumping conduction.”

            Speeding up the Signal

            The velocity of the propagation down the axon is due to how large those myelin sheaths are around the neuron. The larger the neuron and the greater the myelin, the faster the conduction. If your axon was unmyelinated, the conduction would be very slow, and it’s actually very easy to understand why. If you are going to jump from node to node, then the only place you need to change the differential charge is at the spaces in between each node. If you have an unmyelinated axon, then you have to change the charge at each individual point along the axon. Synaptic transmission in myelinated axons is a lot faster than in unmyelinated, because it just jumps from node to node. That’s why you can have a neuron and motor cortex, and you can think that you want to reach out and touch an object and then do it almost instantaneously. Yet those action potentials had to go from motor neurons in your cortex, down to your spinal cord, synapse in the spinal cord and go out to cause contraction of the muscle. But it seems almost instantaneous to us because these are myelinated axons that are very, very fast.

            Our next question is, what happens when the action potential reaches the axon terminal endings? That would seem to be the next place to go. The neuron propagates an action potential to the axon terminals, where they will form synapses with the next cell. What happens here at the synapse?

            Calcium, Neurotransmitters, and Receptors

            See Fig 3. The action potential—the electrical charge—causes a particular thing to happen. It causes the presynaptic membrane, the terminal ending, to open up channels that allow an influx of calcium—one of the charged ions in that extracellular space. When calcium comes into the nerve terminal, it sets up a cascade of events that are going to result in the movement of little vesicles to the membrane termination point. These membranes fuse with the presynaptic membrane and dump their contents—neurotransmitters—out into the cleft, the space that separates one neuron from another neuron.

            The last question is, what happens now in the postsynaptic structure? The only way the first neuron can communicate with the second neuron is through some kind of signal that it can read. And what happens? The action potential causes the release ultimately of neurotransmitter or chemicals from this presynaptic terminal. Those chemicals diffuse across the synaptic cleft to interact with specific receptors on the postsynaptic cell. Interaction of the neurotransmitter with those postsynaptic receptors is going to do one of two things. It’s either going to directly open channels in that postsynaptic membrane—the channel is just a protein that controls the flow of ions across its membrane. Or, it’s going to bind to another molecule that eventually will also result in different ions being distributed across the postsynaptic membrane. We refer to the changes taking place at a synapse as membrane potentials or postsynaptic membrane potentials.

            Grading Postsynaptic Potential

            These potentials are different from action potentials in a number of ways. First of all, they are generated in dendrites and spines. Dendrites are just extensions of the cell body and spines are just protuberances of the dendritic surface to increase the surface area. Synaptic potentials can be depolarizing or hyperpolarizing. In other words, they can be excitatory or inhibitory. But unlike action potentials, synaptic potentials are graded and “decremental.”

            Neurons have a variety of axonal inputs. These are axons coming from different places, other nuclei in the brain, synapsing upon the cell either its cell body or its dendrites or spines. Graded and decremental means that the synaptic potentials, which are generated in the dendrites or spines, are graded in that how big they are depends on how much neurotransmitter got released. Decremental means something interesting. Spines and dendrites are not myelinated. These are true extensions of the cell body surface. And this means that a synapse on the edge of a cell has to change the membrane and ion distribution at each point along the way to the cell body and the axon hillock. That means as that signal is transferred, it decrements, so that it becomes smaller.

            Now what is the consequence of this? What does it mean? Well, it means that it’s the sum of all the excitatory and inhibitory input to this neuron that will ultimately determine whether an action potential will be fired at the axon hillock. There are thousands of synapses coming in and either exciting the postsynaptic membrane or inhibiting the postsynaptic membrane, and then the addition of all these thousands of synapses and their excitation and their inhibition will determine whether an action potential will be generated at the axon hillock. And once that’s generated, that action potential will then be propagated in an all-or-none fashion to a synapse again, and on and on and on in a chain of neurons.

            Common Questions About the Neuron Doctrine

            The Neuron Doctrine was a theory developed in the late 1800’s detailing properties of neurons and the nervous system that explained that neurons were discrete rather than continuous .