26.2 How Neurons Communicate

Learning Objectives

Learning Objectives

In this section, you will explore the following questions:

  • What is the basis of the resting membrane potential?
  • What are the stages of an action potential, and how are action potentials propagated?
  • What are the similarities and differences between chemical and electrical synapses?
  • What is long-term potentiation and long-term depression, and how do both relate to transmission of impulses across synapses?

Connection for AP® Courses

Connection for AP® Courses

The neuron is a great example of a structure-function relationship at the cellular level. Information flow along a neuron is usually from dendrite to axon and from neuron to neuron or from neuron to a cell of a target organ. Like other eukaryotic cells, neurons consist of a cell membrane, nucleus, and organelles, including mitochondria. Action potentials propagate impulses along neurons. When an axon is at rest, the membrane is said to be polarized; that is, there is an electrochemical gradient across it, with the inside of the membrane being more negatively charged than the outside. We explored the formation of electrochemical gradients using H+ when we studied photosynthesis and cellular respiration. The neuron, however, uses Na+ and K+ to establish a gradient. It is also important to recall that ions cannot diffuse across the lipid bilayer of the cell membrane and must use transport proteins; in this case, the transport proteins are voltage-gated Na+ and K+ channels.

At rest, the Na+/K+ pump, powered by ATP, maintains this gradient, known as resting membrane potential. In response to a stimulus, such as an odorant molecule, membrane potential changes, and an action potential is generated along the membrane as the voltage-gated Na+ and K+ channels open sequentially, causing the membrane to depolarize. In depolarization, the inside of the membrane becomes more positive than the outside as Na+ flows to the inside. Repolarization occurs when K+ flows across the membrane to the outside. In myelinated neurons, action potentials jump between gaps of unmyelinated axons, called nodes of Ranvier; a phenomenon called saltatory conduction.

Transmission of a nerve impulse from one neuron to another or to another type of cell such as a muscle cell occurs across a junction called a synapse. Synaptic vesicles at the axon terminal of the presynaptic neuron release chemical messengers called neurotransmitters into the junction; neurotransmitters then bind to receptors embedded in the membrane of the postsynaptic neuron. Neurotransmitters may be either excitatory such as acetylcholine or epinephrine, or inhibitory such as serotonin or GABA, as they either increase or decrease the change of an action potential in the postsynaptic neuron. Many drugs, including both pharmaceuticals and drugs of abuse, can induce changes in synaptic transmission; for example, tetrahydrocannabinol, more commonly known as THC, in marijuana binds to a naturally occurring neurotransmitter important to short-term memory.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP® Biology Curriculum Framework. The AP® Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A learning objective merges required content with one or more of the seven science practices.

Big Idea 3 Living systems store, retrieve, transmit, and respond to information essential to life processes.
Enduring Understanding 3.E Transmission of information results in changes within and between biological systems.
Essential Knowledge 3.E.2 Animals have nervous systems that detect external and internal signals, transmit and integrate information, and produce responses.
Science Practice 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices.
Learning Objective 3.43 The student is able to construct an explanation, based on scientific theories and models, about how nervous systems detect external and internal signals, transmit and integrate information, and produce responses.
Essential Knowledge 3.E.2 Animals have nervous systems that detect external and internal signals, transmit and integrate information, and produce responses.
Science Practice 1.2 The student can describe representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective 3.45 The student is able to describe how nervous systems transmit information.
Essential Knowledge 3.E.2 Animals have nervous systems that detect external and internal signals, transmit and integrate information, and produce responses.
Science Practice 1.1 The student can create representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective 3.47 The student is able to create a visual representation of complex nervous systems to describe/explain how these systems detect external and internal signals, transmit and integrate information, and produce responses.

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.

Nerve Impulse Transmission Within a Neuron

Nerve Impulse Transmission Within a Neuron

For the nervous system to function, neurons must be able to send and receive signals. These signals are possible because each neuron has a charged cellular membrane, which is a voltage difference between the inside and the outside. The charge of this membrane can change in response to neurotransmitter molecules released from other neurons and environmental stimuli. To understand how neurons communicate, one must first understand the basis of the baseline or resting membrane charge.

Neuronal-charged Membranes

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. Ion channels have different configurations: open, closed, and inactive, as illustrated in Figure 26.9. Some ion channels need to be activated in order to open and allow ions to pass into or out of the cell. These ion channels are sensitive to the environment and can change their shape accordingly. Ion channels that change their structure in response to voltage changes are called voltage-gated ion channels. Voltage-gated ion channels regulate the relative concentrations of different ions inside and outside the cell. The difference in total charge between the inside and outside of the cell is called the membrane potential.

The first image shows a voltage-gated sodium channel that is closed at the resting potential. In response to a nerve impulse the channel opens, allowing sodium to enter the cell. After the impulse the channel enters an inactive state. The channel closes by a different mechanism and, for a brief period does not reopen in response to a new nerve impulse.
Figure 26.9 Voltage-gated ion channels open in response to changes in membrane voltage. After activation, they become inactivated for a brief period and will no longer open in response to a signal.

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This video discusses the basis of the resting membrane potential.

Resting Membrane Potential

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. If the membrane were equally permeable to all ions, each type of ion would flow across the membrane and the system would reach equilibrium. Because ions cannot simply cross the membrane at will, there are different concentrations of several ions inside and outside the cell, as shown in Table 26.1. The difference in the number of positively charged potassium ions (K+) inside and outside the cell dominates the resting membrane potential (Figure 26.10). When the membrane is at rest, K+ ions accumulate inside the cell due to a net movement with the concentration gradient. The negative resting membrane potential is created and maintained by increasing the concentration of cations outside the cell in the extracellular fluid, relative to inside the cell in the cytoplasm. The negative charge within the cell is created by the cell membrane being more permeable to potassium ion movement than sodium ion movement. In neurons, potassium ions are maintained at high concentrations within the cell while sodium ions are maintained at high concentrations outside of the cell. The cell possesses potassium and sodium leakage 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. The actions of the sodium potassium pump help to maintain the resting potential, once established. Recall that sodium potassium pumps brings two K+ ions into the cell while removing three Na+ ions per ATP consumed. As more cations are expelled from the cell than taken in, the inside of the cell remains negatively charged relative to the extracellular fluid. It should be noted that calcium 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
Na+ 145 12 12
K+ 4 155 0.026
Cl 120 4 30
Organic anions (A−) 100
Table 26.1 The resting membrane potential is a result of different concentrations inside and outside the cell.
The resting membrane potential of minus seventy volts is maintained by a sodium/potassium transporter that transports sodium ions out of the cell and potassium ions in. Voltage gated sodium and potassium channels are closed. In response to a nerve impulse, some sodium channels open, allowing sodium ions to enter the cell. The membrane starts to depolarize; in other words, the charge across the membrane lessens. If the membrane potential increases to the threshold of excitation, all the sodium channels ope
Figure 26.10 The (a) resting membrane potential is a result of different concentrations of Na+ and K+ ions inside and outside the cell. A nerve impulse causes Na+ to enter the cell, resulting in (b) depolarization. At the peak action potential, K+ channels open and the cell becomes (c) hyperpolarized.

Action Potential

A neuron can receive input from other neurons and, if this input is strong enough, 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. When neurotransmitter molecules bind to receptors located on a neuron’s dendrites, ion channels open. At excitatory synapses, this opening allows positive ions to enter the neuron and results in depolarization of the membrane, which is a decrease in the difference in voltage between the inside and outside of the neuron. A stimulus from a sensory cell or another neuron depolarizes the target neuron to its threshold potential (-55 mV). Na+ channels in the axon hillock open, allowing positive ions to enter the cell as seen in Figure 26.10 and Figure 26.11. Once the sodium channels open, the neuron completely depolarizes to a membrane potential of about +40 mV. Action potentials are considered an all-or nothing event, in that, once the threshold potential is reached, the neuron always completely depolarizes. Once depolarization is complete, the cell must now reset its membrane voltage back to the resting potential. To accomplish this, the Na+ channels close and cannot be opened. This begins the neuron's refractory period, in which it cannot produce another action potential because its sodium channels will not open. At the same time, voltage-gated K+ channels open, allowing K+ to leave the cell. As K+ ions leave the cell, the membrane potential once again becomes negative. The diffusion of K+ out of the cell actually hyperpolarizes the cell, in that the membrane potential becomes more negative than the cell's normal resting potential. At this point, the sodium channels will return to their resting state, meaning they are ready to open again if the membrane potential again exceeds the threshold potential. Eventually the extra K+ ions diffuse out of the cell through the potassium leakage channels, bringing the cell from its hyperpolarized state, back to its resting membrane potential.

Visual Connection

Graph plots membrane potential in millivolts versus time. The membrane remains at the resting potential of -70 millivolts until a nerve impulse occurs in step 1. Some sodium channels open, and the potential begins to rapidly climb past the threshold of excitation of -55 millivolts, at which point all the sodium channels open. At the peak action potential, the potential begins to rapidly drop as potassium channels open and sodium channels close. As a result, the membrane repolarizes past the resting membra
Figure 26.11 The formation of an action potential can be divided into five steps: (1) a stimulus from a sensory cell or another neuron causes the target cell to depolarize toward the threshold potential; (2) if the threshold of excitation is reached, all Na+ channels open and the membrane depolarizes; (3) at the peak action potential, K+ channels open and K+ begins to leave the cell, while at the same time, Na+ channels close; (4) the membrane becomes hyperpolarized as K+ ions continue to leave the cell. The hyperpolarized membrane is in a refractory period and cannot fire. (5) The K+ channels close and the Na+/K+ transporter restores the resting potential.
The action potential travels from the soma down the axon to the axon terminal. The action potential is initiated when a signal from the soma causes the soma-end of the axon membrane to depolarize. The depolarization spreads down the axon. Meanwhile, the membrane at the start of the axon repolarizes. Because potassium channels are open, the membrane cannot depolarize again. The action potential continues to spread down the axon this way.
Figure 26.12 The action potential is conducted down the axon as the axon membrane depolarizes, then repolarizes.

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This video presents an overview of action potential.

Myelin and the Propagation of the Action Potential

For an action potential to communicate information to another neuron, it must travel along the axon and reach the axon terminals where it can initiate neurotransmitter release. The speed of conduction of an action potential along an axon is influenced by both the diameter of the axon and the axon’s resistance to current leak. Myelin acts as an insulator that prevents the current from leaving the axon; this increases the speed of action potential conduction. In demyelinating diseases like multiple sclerosis, action potential conduction slows because current leaks from previously insulated axon areas. The nodes of Ranvier, illustrated in Figure 26.13 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. If nodes of Ranvier were not present along an axon, the action potential would propagate very slowly since Na+ and K+ channels would have to continuously regenerate action potentials at every point along the axon instead of at specific points. 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.

Illustration shows an axon covered in three bands of myelin sheath. Between the sheath coverings the axon is exposed. The uncovered parts of the axon are called nodes of Ranvier. In the illustration, the left node of Ranvier is depolarized such that the membrane potential is positive inside and negative outside. The right membrane of the right node is at the resting potential, negative inside and positive outside. An arrow indicates that the depolarization jumps from the left node to the right, so that th
Figure 26.13 Nodes of Ranvier are gaps in myelin coverage along axons. Nodes contain voltage-gated K+ and Na+ channels. Action potentials travel down the axon by jumping from one node to the next.

Synaptic Transmission

Synaptic Transmission

The synapse or gap is the place where information is transmitted from one neuron to another. Synapses usually form between axon terminals and dendritic spines, but this is not universally true. There are also axon-to-axon, dendrite-to-dendrite, and axon-to-cell body synapses. The neuron transmitting the signal is called the presynaptic neuron, and the neuron receiving the signal is called the postsynaptic neuron. Note that these designations are relative to a particular synapse—most neurons are both presynaptic and postsynaptic. There are two types of synapses: chemical and electrical.

Chemical Synapse

When an action potential reaches the axon terminal it 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+ channels to open. Calcium ions entering the cell initiate a signaling cascade that causes small membrane-bound vesicles, called synaptic vesicles, containing neurotransmitter molecules to fuse with the presynaptic membrane. Synaptic vesicles are shown in Figure 26.14, which is an image from a scanning electron microscope.

The axon terminal is spherical. A section is sliced off, revealing small blue and orange vesicles just inside.
Figure 26.14 This pseudocolored image taken with a scanning electron microscope shows an axon terminal that was broken open to reveal synaptic vesicles, noted in blue and orange, inside the neuron. (credit: modification of work by Tina Carvalho, NIH-NIGMS; scale-bar data from Matt Russell)

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, as illustrated in Figure 26.15. The neurotransmitter diffuses across the synaptic cleft and binds to receptor proteins on the postsynaptic membrane.

Illustration shows a narrow axon of a presynaptic cell widening into a bulb-like axon terminal. A narrow synaptic cleft separates the axon terminal of the presynaptic cell from the postsynaptic cell. In step 1, an action potential arrives at the axon terminal. In step 2, the action potential causes voltage-gated calcium channels in the axon terminal open, allowing calcium to enter. In step 3, calcium influx causes neurotransmitter-containing synaptic vesicles to fuse with the plasma membrane. Contents of
Figure 26.15 Communication at chemical synapses requires release of neurotransmitters. When the presynaptic membrane is depolarized, voltage-gated Ca2+ channels open and allow Ca2+ to enter the cell. The calcium entry causes synaptic vesicles to fuse with the membrane and release neurotransmitter molecules into the synaptic cleft. The neurotransmitter diffuses across the synaptic cleft and binds to ligand-gated ion channels in the postsynaptic membrane, resulting in a localized depolarization or hyperpolarization of the postsynaptic neuron.

The binding of a specific neurotransmitter causes particular ion channels, in this case ligand-gated channels, on the postsynaptic membrane to open. Neurotransmitters can either have excitatory or inhibitory effects on the postsynaptic membrane, as detailed in Table 26.1. 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. This depolarization is called an excitatory postsynaptic potential (EPSP) and makes the postsynaptic neuron more likely to fire an action potential. Release of neurotransmitter at inhibitory synapses causes inhibitory postsynaptic potentials (IPSPs), a hyperpolarization of the presynaptic membrane. For example, when the neurotransmitter GABA is released from a presynaptic neuron, it binds to and opens Cl- channels. Cl- ions enter the cell and hyperpolarizes the membrane, making the neuron less likely to fire an action potential.

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, it can be degraded by enzymes in the synaptic cleft, or it can be recycled (sometimes called reuptake) by the presynaptic neuron. Several drugs act at this step of neurotransmission. For example, some drugs that are given to Alzheimer’s patients work by inhibiting acetylcholinesterase, the enzyme that degrades acetylcholine. This inhibition of the enzyme essentially increases neurotransmission at synapses that release acetylcholine. Once released, the acetylcholine stays in the cleft and can continually bind and unbind to postsynaptic receptors.

Neurotransmitter Examples and Location
Neurotransmitter Example Location
Acetylcholine CNS and/or PNS
Biogenic amine Dopamine, serotonin, norepinephrine CNS and/or PNS
Amino acid Glycine, glutamate, aspartate, gamma aminobutyric acid CNS
Neuropeptide Substance P, endorphins CNS and/or PNS
Table 26.2

Electrical Synapse

While electrical synapses are fewer in number than chemical synapses, they are found in all nervous systems and play important roles. The mode of neurotransmission in electrical synapses is quite different from that in chemical synapses. In an electrical synapse, the presynaptic and postsynaptic membranes are very close together and are actually physically connected by channel proteins forming gap junctions. Gap junctions allow current to pass directly from one cell to the next. In addition to the ions that carry this current, other molecules, such as ATP, can diffuse through the large gap junction pores.

There are key differences between chemical and electrical synapses. Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is unidirectional. Signaling in electrical synapses, in contrast, is virtually instantaneous, which is important for synapses involved in key reflexes, and some electrical synapses are bidirectional. Electrical synapses are also more reliable as they are less likely to be blocked, and they are important for synchronizing the electrical activity of a group of neurons. For example, electrical synapses in the thalamus are thought to regulate slow-wave sleep, and disruption of these synapses can cause seizures.

Signal Summation

Signal Summation

Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron, but often 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 in Figure 26.16. Additionally, one neuron often has both excitatory and inhibitory inputs from many presynaptic neurons—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.

Illustration shows the location of the axon hillock, which is the area connecting the neuron body to the axon. A graph shows the summation of membrane potentials at the axon hillock, plotted as membrane potential in millivolts versus time. Initially, the membrane potential at the axon hillock is -70 millivolts. A series of EPSPs and IPSPs cause the potential to rise and fall. Eventually, the potential increases to the threshold of excitation. At this point the nerve fires, resulting in a sharp increase in
Figure 26.16 A single neuron can receive both excitatory and inhibitory inputs from multiple neurons, resulting in local membrane depolarization (EPSP input) and hyperpolarization (IPSP input). All these inputs are added together at the axon hillock. If the EPSPs are strong enough to overcome the IPSPs and reach the threshold of excitation, the neuron will fire.

Everyday Connection

Brain-computer interface

Amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s Disease) is a neurological disease characterized by the degeneration of the motor neurons that control voluntary movements. The disease begins with muscle weakening and lack of coordination and eventually destroys the neurons that control speech, breathing, and swallowing; in the end, the disease can lead to paralysis. At that point, patients require assistance from machines to be able to breathe and to communicate. Several special technologies have been developed to allow locked-in patients to communicate with the rest of the world. One technology, for example, allows patients to type out sentences by twitching their cheek. These sentences can then be read aloud by a computer.

A relatively new line of research for helping paralyzed patients, including those with ALS, to communicate and retain a degree of self-sufficiency is called brain-computer interface (BCI) technology and is illustrated in Figure 26.17. This technology sounds like something out of science fiction: It allows paralyzed patients to control a computer using only their thoughts. There are several forms of BCI. Some forms use EEG recordings from electrodes taped onto the skull. These recordings contain information from large populations of neurons that can be decoded by a computer. Other forms of BCI require the implantation of an array of electrodes smaller than a postage stamp in the arm and hand area of the motor cortex. This form of BCI, while more invasive, is very powerful as each electrode can record actual action potentials from one or more neurons. These signals are then sent to a computer, which has been trained to decode the signal and feed it to a tool such as a cursor on a computer screen. This means that a patient with ALS can use email read the internet and communicate with others by thinking of moving his or her hand or arm even though the paralyzed patient cannot make that bodily movement. Recent advances have allowed a paralyzed locked-in patient who suffered a stroke 15 years ago to control a robotic arm and even to feed herself coffee using BCI technology.

Despite the amazing advancements in BCI technology, it also has limitations. The technology can require many hours of training and long periods of intense concentration for the patient; it can also require brain surgery to implant the devices.

Illustration shows a person in a wheelchair, facing a computer screen. An arrow indicates that neural signals travel from the brain of the paralyzed person to the computer.
Figure 26.17 With brain-computer interface technology, neural signals from a paralyzed patient are collected, decoded, and then fed to a tool, such as a computer, a wheelchair, or a robotic arm.

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Watch this video in which a paralyzed woman use a brain-controlled robotic arm to bring a drink to her mouth, among other images of brain-computer interface technology in action.

Synaptic Plasticity

Synaptic Plasticity

Synapses are not static structures. They can be weakened or strengthened. They can be broken, and new synapses can be made. Synaptic plasticity allows for these changes, which are all needed for a functioning nervous system. In fact, synaptic plasticity is the basis of learning and memory. Two processes in particular, long-term potentiation (LTP) and long-term depression (LTD) are important forms of synaptic plasticity that occur in synapses in the hippocampus, a brain region that is involved in storing memories.

Long-term Potentiation (LTP)

Long-term potentiation (LTP) is a persistent strengthening of a synaptic connection. LTP is based on the Hebbian principle: cells that fire together wire together. There are various mechanisms, none fully understood, behind the synaptic strengthening seen with LTP. One known mechanism involves a type of postsynaptic glutamate receptor, called NMDA (N-Methyl-D-aspartate) receptors, shown in Figure 26.18. These receptors are normally blocked by magnesium ions; however, when the postsynaptic neuron is depolarized by multiple presynaptic inputs in quick succession, either from one neuron or multiple neurons, the magnesium ions are forced out allowing Ca2+ ions to pass into the postsynaptic cell. Next, Ca2+ ions entering the cell initiate a signaling cascade that causes a different type of glutamate receptor, called AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, to be inserted into the postsynaptic membrane, since activated AMPA receptors allow positive ions to enter the cell. So, the next time glutamate is released from the presynaptic membrane, it will have a larger excitatory effect on the postsynaptic cell because the binding of glutamate to these AMPA receptors will allow more positive ions into the cell. The insertion of additional AMPA receptors strengthens the synapse and means that the postsynaptic neuron is more likely to fire in response to presynaptic neurotransmitter release.

Long-term Depression (LTD)

Long-term depression (LTD) is essentially the reverse of LTP: It is a long-term weakening of a synaptic connection. One mechanism known to cause LTD also involves AMPA receptors. In this situation, calcium that enters through NMDA receptors initiates a different signaling cascade, which results in the removal of AMPA receptors from the postsynaptic membrane, as illustrated in Figure 26.18. The decrease in AMPA receptors in the membrane makes the postsynaptic neuron less responsive to glutamate released from the presynaptic neuron. While it may seem counterintuitive, LTD may be just as important for learning and memory as LTP. The weakening and pruning of unused synapses allows for unimportant connections to be lost and makes the synapses that have undergone LTP that much stronger by comparison.

Illustration shows the mechanism of LTP and LTD. Normally, the NMDA receptor in the postsynaptic neuron is activated by glutamate binding, but only after depolarization removes an inhibitory magnesium ion. Once the magnesium is removed, calcium can enter the cell. In response to an increase in intracellular calcium, AMPA receptors are inserted into the plasma membrane, which amplifies the signal resulting in LTP. LDP occurs when low-frequency stimulation results in the activation of a different calcium-si
Figure 26.18 Calcium entry through postsynaptic NMDA receptors can initiate two different forms of synaptic plasticity: LTP and LTD. LTP arises when a single synapse is repeatedly stimulated. This stimulation causes a calcium- and CaMKII-dependent cellular cascade, which results in the insertion of more AMPA receptors into the postsynaptic membrane. The next time glutamate is released from the presynaptic cell, it will bind to both NMDA and the newly inserted AMPA receptors, thus depolarizing the membrane more efficiently. LTD occurs when few glutamate molecules bind to NMDA receptors at a synapse due to a low firing rate of the presynaptic neuron). The calcium that does flow through NMDA receptors initiates a different calcineurin and protein phosphatase 1-dependent cascade, which results in the endocytosis of AMPA receptors. This makes the postsynaptic neuron less responsive to glutamate released from the presynaptic neuron.

Science Practice Connection for AP® Courses

Activity

Don’t Eat the Fugu: Understanding the Neuron. Create a model of a neuron to explain how the vertebrate nervous system detects signals and transmits information. Then use the model to predict how abnormal cell structure, drugs, and toxins such as tetrodotoxin found in fugu/pufferfish can affect impulse transmission.

Think About It

Potassium channel blockers, such as procainamide, are often used to treat abnormal activity in the heart. These channel blocks impede the movement of K+ through voltage-gated K+ channels. What is the likely effect(s) of these medications on action potentials?

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