- Describe the structure and function of neurons
- Interpret an action potential graph and explain the molecular mechanisms underlying each step of the action potential
- Describe the structure and function of neuronal synapses and the role of neurotransmitters at the synapse
Neurons and Glial Cells
The nervous system is made up of neurons, the specialized cells that can receive and transmit chemical or electrical signals, and glia, the cells that provide support functions for the neurons. A neuron can be compared to an electrical wire: it transmits a signal from one place to another. Glia can be compared to the workers at the electric company who make sure wires go to the right places, maintain the wires, and take down wires that are broken. Recent evidence suggests that glia may also assist in some of the signaling functions of neurons.
Neurons communicate via both electrical signals and chemical signals. The electrical signals are action potentials, which transmit the information from one of a neuron to the other; the chemical signals are neurotransmitters, which transmit the information from one neuron to the next. An action potential is a rapid, temporary change in membrane potential (electrical charge), and it is caused by sodium rushing to a neuron and potassium rushing out. Neurotransmitters are chemical messengers which are released from one neuron as a result of an action potential; they cause a rapid, temporary change in the membrane potential of the adjacent neuron to initiate an action potential in that neuron.
Parts of a Neuron
Like other cells, each neuron has a cell body (or soma) that contains a nucleus and other cellular components. Neurons also contain unique structures, dendrites and axons, for receiving and sending the electrical signals that make neuronal communication possible:
- Dendrites: are tree-like structures that extend away from the cell body to receive neurotransmitters from other neurons. Some types of neurons do not have any dendrites, some types of neurons have multiple dendrites. Dendrites can have small protrusions called dendritic spines, which further increase surface area for possible connections with other neurons.
- Synapses: Dendrites receive signals from other neurons at specialized junctions called synapses. There is a small gap between two synapsed neurons, where neurotransmitters are released from one neuron to pass the signal to the next neuron.
- Axon hillock: Once a signal is received by the dendrite, it then travels to the cell body. The cell body contains a specialized structure, the axon hillock that “integrates” signals from multiple synapses and serves as a junction between the cell body and an axon.
- Axon: An axon is a tube-like structure that propagates the integrated signal to specialized endings called axon terminals. The axon carries the action potential to the next neuron. Neurons usually have one or two axons. Some axons are covered with myelin, which acts as an insulator to minimize dissipation of the electrical signal as it travels down the axon, greatly increasing the speed on conduction. This insulation is important as the axon from a human motor neuron can be as long as a meter, from the base of the spine to the toes. The myelin sheath is not actually part of the neuron, and is produced by glial cells. Along the axon there are periodic gaps in the myelin sheath called nodes of Ranvier, which are sites where the signal is “re-charged” as it travels along the axon.
It is important to note that a single neuron does not act alone: neuronal communication depends on the connections that neurons make with one another (as well as with other cells, like muscle cells). Dendrites from a single neuron may receive synaptic contact from many other neurons. For example, dendrites from a neurons in the cerebellum of the brain are thought to receive contact from as many as 200,000 other neurons.
While glia are often thought of as the supporting cast of the nervous system, the number of glial cells in the brain actually outnumbers the number of neurons by a factor of ten. Neurons would be unable to function without the vital roles that are fulfilled by these glial cells. Glia guide developing neurons to their destinations, buffer ions and chemicals that would otherwise harm neurons, provide myelin sheaths around axons, and modulate communication between nerve cells. When glia do not function properly, the result can be disastrous; most brain tumors are caused by mutations in glia.
There are several different types of glia with different functions. They include:
- Astrocytes: provide nutrients and other substances to neurons, regulate the concentrations of ions and chemicals in the extracellular fluid, and provide structural support for synapses; also form the blood-brain barrier, which blocks entrance of toxic substances into the brain.
- Satellite glia: nutrients and structural support for neurons in the peripheral nervous system (PNS).
- Microglia: immune cells of the central nervous system (CNS); scavenge and degrade dead cells and protect the brain from invading microorganisms.
- Oligodendrocytes: form myelin sheaths around axons in the CNS; one axon can be myelinated by several oligodendrocytes, and one oligodendrocyte can provide myelin for multiple neurons.
- Schwann cells: form myelin sheaths around axons in the PNS; unlike oligodendrocytes, a single Schwann cell provides myelin for only one axon as the entire Schwann cell surrounds the axon.
- Ependymal cells: line fluid-filled ventricles of the brain and the central canal of the spinal cord; help circulate cerebrospinal fluid, which serves as a cushion for the brain.
Communication Between Neurons
All functions performed by the nervous system – from a simple motor reflex to more advanced functions like making a memory or a decision – require neurons to communicate with one another. While humans use words and body language to communicate, neurons use electrical and chemical signals. Just like a person in a committee, one neuron usually receives and synthesizes messages from multiple other neurons before “making the decision” to send the message on to other neurons.
Neurons communicate via both electrical and chemical signals. A neuron receives input from other neurons and, if this input is strong enough, the neuron will send the signal to downstream neurons. Transmission of a signal between neurons is generally carried by a chemical called a neurotransmitter. Transmission of a signal within a neuron (from dendrite to axon terminal) is carried by a brief reversal of the resting membrane potential called an action potential. This communication is possible because each neuron has a charged cellular membrane (a voltage difference between the inside and the outside), and the charge of this membrane can change in response to neurotransmitter molecules released from other neurons and environmental stimuli. The three general phenomena required for communication between neurons are:
- Resting potential: the membrane potential (electrical charge) in a neuron that is not currently transmitting a signal
- Action potential: a brief depolarizaiton (reduction in magnitude of the charge) along the neuron’s axon; action potentials are all-or-nothing (they do not have degrees of magnitude)
- Neurotransmitters: the chemical messengers that communicate between adjacent neurons; release of neurotransmitters from one neuron will either help depolarize or hyperpolarize (increase the magnitude of the charge) the adjacent neuron, making an action potential either more or less likely to occur in the next neuron
We’ll discuss each of these three components in turn.
1. The Resting Potential
The lipid bilayer membrane that surrounds a neuron is impermeable to charged molecules or ions. To enter or exit the neuron, ions must pass through special proteins called ion channels that span the membrane and regulate the relative concentrations of different ions inside and outside the cell. Cells can use energy to preferentially move certain ions either inside or outside of the membrane, setting up a difference in ion charge across the membrane, where one side is relatively more negative and the other side is relatively more positive. The difference in total charge between the inside and outside of the cell is called the membrane potential.
The membrane potential of a neuron at rest is negatively charged: the inside of a cell is approximately 70 millivolts more negative than the outside (-70 mV, note that this number varies by neuron type and by species). This voltage is called the resting membrane potential; it is caused by differences in the concentrations of ions inside and outside the cell. The resting potential is established and maintained by two main processes: an ATP-powered ion channel called the sodium-potassium pump, and a passive ion channel called the potassium leak channel.
The sodium-potassium pump, which is also called Na+/K+ ATPase, transports sodium out of a cell while moving potassium into the cell. The Na+/K+ pump is an important ion pump found in the membranes of many types of cells. These pumps are particularly abundant in nerve cells, which are constantly pumping out sodium ions and pulling in potassium ions to maintain an electrical gradient across their cell membranes. An electrical gradient is a difference in electrical charge across a space. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively-charged (at around -70 mV) relative to the outside. The negative electrical gradient is maintained because each Na+/K+ pump moves three Na+ ions out of the cell and two K+ ions into the cell for each ATP molecule that is used. This process is so important for nerve cells that it accounts for the majority of their ATP usage.
In addition to the sodium potassium pump, neurons possess potassium leak channels and sodium leak channels that allow the two cations to diffuse down their concentration gradient. However, the neurons have far more potassium leakage channels than sodium leakage channels. Therefore, potassium diffuses out of the cell at a much faster rate than sodium leaks in. Because more cations are leaving the cell than are entering, this causes the interior of the cell to be negatively charged relative to the outside of the cell. Thus the combined effects of the sodium-potassium pump and the potassium leak channels is that the interior of the cell is more negative than the outside of the cell. It should also be noted that chloride ions (Cl–) tend to accumulate outside of the cell because they are repelled by negatively-charged proteins within the cytoplasm.
|Ion Concentration Inside and Outside Neurons|
|Ion||Extracellular concentration (mM)||Intracellular concentration (mM)||Ratio outside/inside|
|Organic anions (A-)||—||100|
This video describes the role of the sodium/potassium pump and potassium leak channels in establishing and maintaining the membrane resting potential:
2. The Action Potential
When we talk about neurons “firing” or being “active,” we’re talking about the action potential: a brief, positive change in the membrane potential along a neuron’s axon. When an action potential occurs, the neuron sends the signal to the next neuron in the communication chain, and, if an action potential also occurs in the next neuron, then the signal will continue being transmitted. What causes an action potential? When a neuron receives a signal from another neuron (in the form of neurotransmitters, for most neurons), the signal causes a change in the membrane potential on the receiving neuron. The signal causes opening or closing of voltage-gated ion channels, channels that open or close in response to changes in the membrane voltage. The opening of voltage-gated ion channels causes the membrane to undergo either a hyperpolarization, where the membrane potential increases in magnitude (becomes more negative) or a depolarization, where the membrane potential decreases in magnitude (becomes more positive). Whether the membrane undergoes a hyperpolarization or a depolarization depends on the type of voltage-gated ion channel that opened.
Not all depolarizations result in an action potential. The signal must cause a depolarization that is large enough in magnitude to overcome the threshold potential, or the specific voltage that the membrane must reach for an an action potential to occur. The threshold potential is usually about -55 mV, compared to the resting potential of about -70 mV. If the threshold potential is reached, then an action potential is initiated at the axon hillock in the following stages:
- Depolarization: voltage-gated sodium channels open quickly after depolarization past the threshold potential. As sodium rushes into the axon (influx), the inside becomes relatively electrically positive (approximately +30 mV, compared to the initial resting potential of apprximately -70 mV).
- Repolarization: shortly after the initial depolarization, the voltage-gated sodium channels close and remain closed (and cannot be opened) for about 1-2 milliseconds. Voltage-gated potassium channels then open, allowing potassium to rush out of the axon (efflux), causing the membrane to repolarize (become more negative).
- Hyperpolarizaton: potassium continues leaving the axon to the point that the membrane potential dips below the normal resting potential. Sodium channels return to their resting state, meaning they are ready to open again if the membrane potential again exceeds the threshold potential.
- Reset resting potential: The sodium-potassium pump and potassium leak channels reset the locations of sodium and potassium ions, reestablishing the membrane potential to allow another action potential to fire.
These steps are illustrated here:
There are a few important universal features of action potentials:
- The action potential travels down the axon, proceeding as a wave of depolarization. The image above shows a trace of an action potential at a single point in the membrane of an axon; the same pattern repeats down the entire length of the axon until it reaches the synapse, shown here:
- Action potentials always proceed in one direction only, from the cell body (soma) to the synapse(s) at the end of the axon. Action potentials never go backward, due to the refractory period of the voltage-gated ion channels, where the channels cannot re-open for a period of 1-2 milliseconds after they have closed. The refractory period forces the action potential to travel only in one direction.
- Action potentials do not vary in magnitude or speed; they are “all-or-nothing.” When a given neuron fires, the action potential always depolarizes to the same magnitude and always travels at the same speed along the axon. There is no such thing as a bigger or faster action potential. The parameter that can vary is the frequency of action potentials, or how many action potentials occur in a given amount of time.
The video below provides a discussion of voltage-gated ion channels:
Here is a more detailed discussion of the action potential trace:
And an overview of action potential propagation:
As noted above, the magnitude or speed of the action potential for a given neuron never varies; however, some neurons have faster action potentials than others. In invertebrates, this difference is often due to axon diameter, where larger axons have faster conduction of action potentials. In vertebrates, this difference is typically due to myelination of the neuron’s axon. Myelin acts as an insulator that prevents current from leaving the axon; this increases the speed of action potential conduction. The nodes of Ranvier, illustrated below, are gaps in the myelin sheath along the axon. These unmyelinated spaces are about one micrometer long and contain voltage gated Na+ and K+ channels. Flow of ions through these channels, particularly the Na+ channels, regenerates the action potential over and over again along the axon. This “jumping” of the action potential from one node to the next is called saltatory conduction. Nodes of Ranvier also save energy for the neuron since the channels only need to be present at the nodes and not along the entire axon.
3. The Chemical Synapse and Neurotransmitters
Neurons are not in direct physical contact with each other, but instead come into very close proximity at a structure called the synapse. The neuron sending a signal to the next is called the presynaptic neuron, and the neuron receiving a signal is called the postsynaptic neuron, shown here:
There is a small gap between the two neurons called the synaptic cleft, where neurotransmitters are released by the presynaptic neuron to transmit the signal to the postsynaptic neuron, shown here:
How does synaptic transmission work? Once the action potential reaches the end of the axon, it propagates into the pre-synaptic terminal where the following events occur in sequence:
- The action potential depolarizes the membrane and opens voltage-gated Na+ channels. Na+ ions enter the cell, further depolarizing the presynaptic membrane.
- This depolarization causes voltage-gated Ca2+ (calcium) channels to open in the presynaptic neuron, allowing calcium ions to enter the presynaptic neuron at the synpase.
- Calcium ions entering the presynaptic neuron cell initiate a signaling cascade that causes small membrane-bound vesicles, called synaptic vesicles, to fuse with the presynaptic membrane. The synaptic vesicles contain neurotransmitter molecules.
- Fusion of a vesicle with the presynaptic membrane causes neurotransmitter to be released into the synaptic cleft, the extracellular space between the presynaptic and postsynaptic membranes. The neurotransmitter diffuses across the synaptic cleft and binds to receptor proteins on the postsynaptic membrane.
This process is illustrated below:
- Excitatory postsynaptic potentials (EPSPs) make a postsynaptic neuron more likely to fire an action potential. For example, when acetylcholine is released at the synapse between a nerve and muscle (called the neuromuscular junction) by a presynaptic neuron, it causes postsynaptic Na+ channels to open. Na+ enters the postsynaptic cell and causes the postsynaptic membrane to depolarize.
- Inhibitory postsynaptic potentials (IPSPs) make a postsynaptic neuron less likely to fire an action potential. For example, when the neurotransmitter GABA (gamma-aminobutyric acid) is released from a presynaptic neuron, it binds to and opens Cl– channels. Cl– ions enter the cell and hyperpolarizes the membrane.
Once neurotransmission has occurred, the neurotransmitter must be removed from the synaptic cleft so the postsynaptic membrane can “reset” and be ready to receive another signal. This can be accomplished in three ways:
- the neurotransmitter can diffuse away from the synaptic cleft
- the neurotransmitter can be degraded by enzymes in the synaptic cleft
- the neurotransmitter can be recycled (sometimes called reuptake) by the presynaptic neuron.
This video walks through the process of signal communication across a chemical synapse:
While action potentials are “all-or-nothing,” as noted above, EPSPs and IPSPs are graded; they vary in magnitude of depolarization or hyperpolarization, as illustrated below:
Often a single EPSP is not strong enough to induce an action potential in the postsynaptic neuron on its own, and multiple presynaptic inputs must create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential. This process is called summation and occurs at the axon hillock, as illustrated below. In addition, each neuron often has inputs from many presynaptic neuron – some excitatory and some inhibitory – so IPSPs can cancel out EPSPs and vice versa. It is the net change in postsynaptic membrane voltage that determines whether the postsynaptic cell has reached its threshold of excitation needed to fire an action potential. Together, synaptic summation and the threshold for excitation act as a filter so that random “noise” in the system is not transmitted as important information.
This video, added after the IKE was opened, provides an overview of summation in time and space:
Here are two final videos to help you put this all together (in a more engaging way than any of the videos above). Note that these videos do not provide any new information, but they may help you better integrate all the information previously discussed: