Hi, welcome back to perceptual motor, motivation, and emotion. In the last few videos, you had already been introduced to the concept of a synapse, as well as the history of the discovery of the synapse. You've also heard explanations about neurotransmitters, or the chemical molecules released at the synapse.
In the next two videos, you will be given more detailed explanations about the sequence of chemical events that occur at the synapse. The material for the video is obtained from the Collat textbook, Chapter 2, Module 2.2. So what exactly are the chemical events that happen at the synapse? First, neurons synthesize chemicals that will become neurotransmitters. Small neurotransmitters are synthesized at the axon terminal, while large neurotransmitters such as peptides are synthesized in the cell body.
Then, when the action potential that occurs along the axon reaches the presynaptic terminal, the action potential will cause calcium, which is more concentrated outside the cell, to enter the cell. The entry of calcium into the cell subsequently causes the release of neurotransmitters into the synaptic cleft. Upon release from the presynaptic terminal, neurotransmitter molecules cross the synaptic gap, known also as the synaptic cleft, and then attach to specialized receptors located on the membrane of the postsynaptic neuron. The binding of neurotransmitter molecules onto these receptors will automatically change or alter the activity of the postsynaptic neuron. In the next stage, once neurotransmitters have completed their task of changing the activity of the postsynaptic neurons, the neurotransmitter molecules will break away from the receptors.
The neurotransmitter molecules will next have to be inactivated. Inactivation of neurotransmitters can occur through the process of reuptake, or reabsorption of neurotransmitter molecules by presynaptic neurons, or through degradation by special enzymes that convert neurotransmitter molecules into inactive fragments. At the end of the process, the postsynaptic neuron will send feedback to the presynaptic neuron to stop further release of neurotransmitters by the presynaptic neuron.
Next, we will look at a video that depicts each of these six events in greater detail. At a chemical synapse, a neurotransmitter molecule, such as acetylcholine, communicates a signal from one neuron, the presynaptic cell, to another, the postsynaptic cell. Neurotransmitter molecules are stored in vesicles in the presynaptic neuron. Some vesicles dock, via specific docking proteins, at the presynaptic terminal.
An electric impulse, called an action potential, arrives at the synaptic terminal and docked vesicles fuse with the presynaptic membrane, dumping neurotransmitter into the synaptic cleft. Neurotransmitter binds receptors on the postsynaptic cell, which, depending on the specific receptor and cell type, open or close ion channels. Thus, the action potential passes to the new cell.
The empty vesicles are recycled via endocytosis of clathrin-coated pits and take up more neurotransmitter, to start the cycle again. As previously described, the first step in the transmission of a chemical message at the synapse begins with the arrival of an action potential at the presynaptic terminal. This action potential triggers the opening of calcium ion channels that are abundant in the presynaptic terminal membrane. With the opening of calcium channels, Calcium ions also rush into the cell. This happens because, like sodium, calcium is also more concentrated outside than inside the cell.
So calcium ions are naturally attracted to the inside of the cell. Calcium that enters the cell then signals the synaptic vesicles, located within the presynaptic terminals, to fuse with the presynaptic terminal's membrane. The fusion of the vesicle then causes the release of neurotransmitter molecules stored in the vesicles into the synaptic cleft through a process known as exocytosis. In general, each neuron releases not only one type of neurotransmitter, but a combination of several neurotransmitters instead. In some neurons, several types of neurotransmitters can even be found in the same presynaptic terminal.
In others, several types of small neurotransmitters are stored in the same vesicle. Meanwhile, some other neurons may release one type of neurotransmitter from one axon terminal, and another type of neurotransmitter molecules from another axon terminal. Such wide variations in the release of neurotransmitters allows neurons to send complex messages, thereby contributing to complex behaviors. In the previous slide, it was explained that the neurotransmitter molecules released by the presynaptic neuron then cross the synaptic cleft.
After crossing the synaptic cleft, neurotransmitter molecules arrive at the membrane of the postsynaptic neuron, where they bind with receptors, which are a special type of proteins embedded in the surface of the postsynaptic membrane. What then happens to the postsynaptic neuron after the neurotransmitter molecule attaches to the receptor? on the type of receptor involved.
In general, the responses of the postsynaptic neurons can appear in the form of either ionotropic effects or metabotropic effects. But before we look at the differences between the ionotropic effect and the metabotropic effect I just mentioned, please pay attention to the image that you currently see on your screen. The image on the left shows a receptor that is responsible for producing an ionotropic effect and is often referred to as an ionotropic receptor, while the picture on the right is a metabotropic receptor.
As you can see, both ionotropic and metabotropic receptors have a special site to which the neurotransmitter molecule attaches. An ionotropic effect occurs when a neurotransmitter molecule attaches to an ionotropic receptor. Activation of the ionotropic receptor by a neurotransmitter molecule causes a change in the shape of the receptor in such a way that would allow charged ions, such as sodium, to enter the cell.
And, as you learned earlier, the influx of charged ions is precisely what causes a change in the polarization of the neuronal membrane. Ionotropic receptors have a lot in common with the sodium and potassium channels discussed last week because they both allow charged ions, such as sodium and potassium, to pass through the neuronal membrane. However, while the sodium and potassium channels in the axons are voltage-gated and will only open up when the oxygen is released, when there is a change in membrane voltage that's large enough to reach excitation threshold, ionotropic receptors are transmitter gated because they only open when neurotransmitter molecules bind to them.
The ionotropic effect occurs quickly, usually beginning a few milliseconds after the neurotransmitter molecule attaches to the receptor. In addition, An ionotropic effect is usually relatively brief in duration, lasting only a few milliseconds. Activation of several ionotropic receptors produces an excitatory effect, or an EPSP, on the postsynaptic neuron, while other ionotropic receptors, when activated, produce inhibitory effects, resulting in an IPSP. In the brain, most of the excitatory ionotropic receptors are activated by the neurotransmitters glutamate and acetylcholine, while the inhibitory ionotropic receptors generally respond to the binding of the neurotransmitters GABA and glycine. Please watch the following video to better understand the mechanisms of action of an ionotropic receptor.
In the video, the ionotropic receptor is referred to as an ion-channel coupled receptor. because of its dual function as an ion channel. Ion channel coupled receptors are embedded in the postsynaptic membrane.
They are comprised of two functional part domains. An extracellular domain that is exposed to the synaptic cleft and thus binds neurotransmitters and a transmembrane or membrane-spanning domain that forms an ion channel. As neurotransmitter binds to the extracellular domain of the receptor, A structural change in the receptor occurs.
Finally, the structural change results in opening or closing of the ion channel, allowing ions to enter or exit the cell. As neurotransmitters transduce an electrical signal into a chemical signal, receptors transduce the chemical signal back into an electrical one. Both glutamate and GABA are examples of neurotransmitters that mediate their effects through ion-channel coupled receptors.
Unlike ionotropic receptors, metabotropic receptors do not function as ion channels. That is, activation of a metabotropic receptor does not cause rapid reactions involving the entry and exit of charged ions. Metabotropic effects involve a number of metabolic reactions that occur sequentially. Thus, when compared with an ionotropic effect, A metabotropic effect tends to be slower and usually lasts longer. While the majority of ionotropic effects are triggered by the neurotransmitters glutamate, acetylcholine, GABA, and glycine, metabotropic receptors respond to a wider variety of neurotransmitters.
In the previous slide, it was mentioned that a metabotropic effect involves a sequence of metabolic reactions that last longer. In particular, when a neurotransmitter attaches itself to a metabotropic receptor, the part of the receptor located on the inside of the neuron activates a G-protein, and this G-protein is responsible for increasing the concentration of second messengers, which are essentially information-sending molecules contained within cells. These second messengers subsequently transmit information to other structures in the cell, and the information carried by second messengers can result in a range of effects, such as the activation of nearby ion channels or the activation of enzymes in neurons.
Second messengers may also alter the production of proteins by cells, or can possibly activate certain parts of the cell's chromosomes. In the next animation clip, you will see how metabotropic receptors work. Note that in the clip, the metabotropic receptor is described as a G-protein coupled receptor. G-protein coupled neurotransmitter receptors do not have ion channels as part of their structure.
Instead, they function through intermediary molecules called G-proteins. These receptors also have two domains. As before, an extracellular domain binds neurotransmitters. However, here, an intracellular domain binds two G-proteins.
Neurotransmitter binding activates the receptor, which in turn activates the G-proteins. G-proteins then dissociate from the receptor. At this point, G-proteins can either interact directly with ion channels, or bind to other proteins, such as enzymes, that go on to open with ion channels. Most of the biogenic amines and peptide neurotransmitters signal through G-protein-coupled receptors. In the short animation you just watched, it was mentioned that one type of neurotransmitter that commonly attaches to a metabotropic receptor is a neuropeptide.
Neuropeptides are categorized as a separate class of chemical messengers in the brain because there are some significant differences between neuropeptides and other neurotransmitters. While other neurotransmitters are generally synthesized at the presynaptic terminals, neuropeptides are synthesized in the cell body before they are transported to other areas of the cell. In addition, Neuropeptides are not released from the presynaptic terminals, but rather from the dendrites, cell body, and the sides of the axon. Furthermore, if one action potential is sufficient to cause the release of a neurotransmitter, for neuropeptides, several repeated stimulations are needed to cause the release.
In general, the effects of neuropeptides also last longer, and therefore, neuropeptides play a bigger role in longer-term changes in behavior, like hunger or thirst. After the neurotransmitters have completed their task of activating the postsynaptic receptors, they are then inactivated to prevent them from unnecessarily continuing to excite or to inhibit the postsynaptic neurons. There are several mechanisms through which neurotransmitters are inactivated.
A neuropeptide, for example, is not completely inactivated and simply leaves the synaptic cleft. after it's finished conveying its message. Several other neurotransmitters are broken down into inactive molecules by enzymes located in the synaptic cleft. In addition, there are neurotransmitters that are completely reabsorbed by the presynaptic neuron.
This reabsorption process is referred to as reuptake and can occur with the help of transporters which are specialized proteins located on the membrane of the presynaptic neuron. The reuptake process allows presynaptic neurons to recycle neurotransmitter molecules for later use. Next, I'd like to ask you to imagine what your reaction would be if a friend called your name over and over or sent you an email with the same message over and over again.
What do you need to do to stop the same message from being sent over and over again? To avoid repeatedly receiving the same message that you've already received, you would most likely opt to respond to the call or email in an attempt to notify your friend that the message has been properly received. The same principle applies to synapses. To prevent the repetition of messages that have already been sent, there are two mechanisms used by cells in the nervous system. The first mechanism is found in presynaptic neurons.
Many presynaptic neurons have autoreceptors on their presynaptic terminals. Autoreceptors are specialized receptors whose job is to track the amount of neurotransmitters that have been released and to then block further synthesis and release of neurotransmitters when sufficient amounts are already released. The second mechanism involves the release of a special chemical by the postsynaptic neuron.
This special chemical signals the presynaptic neuron to stop the further release of neurotransmitter molecules. To summarize, And to enhance your comprehension of the sequence of events taking place at the synapse, please watch the following animation. Communication between neurons occurs at specialized junctions called synapses. The most common type of synapse is the chemical synapse. In this tutorial, we will examine the events that take place at a typical chemical synapse in the central nervous system.
Synaptic transmission begins when the nerve impulse reaches the presynaptic axon terminal. Depolarization of the presynaptic membrane initiates the sequence of events leading to transmitter release and activation of receptors on the postsynaptic membrane. Shown here are the principal molecules and organelles necessary for release of neurotransmitter.
When the axon terminal is depolarized, voltage-gated calcium channels open. and calcium ions rush into the axon terminal. Some of the calcium ions bind to a protein on the synaptic vesicle membrane called synaptotagmin. When calcium binds to synaptotagmin on the synaptic vesicles nearest the active zone of the synapse, the vesicles move toward the presynaptic membrane. The membranes of the synaptic vesicles and the axon terminal membrane are drawn together via protein complexes, collectively called snares.
that are expressed on the vesicle and presynaptic membranes. When the vesicles fuse with the axon terminal membrane, they release their transmitter molecules into the synaptic cleft. Normally, a nerve impulse causes the release of several hundred vesicles at a time. Some of the transmitter molecules bind to special receptor molecules in the postsynaptic membrane. The response of the postsynaptic cell, for example excitation or inhibition, depends upon the particular neurotransmitter and receptor combination.
For example, the receptor for acetylcholine is a sodium ion channel. After binding acetylcholine, The channel opens and sodium ions enter the postsynaptic cell, thereby generating an excitatory postsynaptic response. Transmitters are inactivated or removed rapidly from the synaptic cleft so that transmission is brief and accurately follows the presynaptic input signal. For acetylcholine, an enzyme in the synaptic cleft, acetylcholine esterase, breaks down acetylcholine into acetyl-CoA and choline.
The release of transmitter from the receptors causes the channels to close. Not all transmitters are broken down by enzymes in the synaptic cleft. Many transmitters are rapidly cleared from the synaptic cleft by being taken up into the presynaptic terminal by special proteins called transporters.
This process is known as reuptake. Reuptake not only cuts off the synaptic activity promptly, but also allows the terminal to recycle transmitter molecules. The membrane needed for creating synaptic vesicles is also recycled via endocytosis of the presynaptic membrane. The recycled vesicles are refilled with neurotransmitter molecules and are ready for another round of synaptic transmission. Up to this point, you should now be able to grasp the extent to which chemical messages play a role at synapses.
Although chemical synapses are the most common type of synapse in the nervous system, there are some exceptions. In some synapses with specialized functions, messages between neurons are transmitted via electrical signals, and the transmission of these electrical messages takes place at gap junctions. Unlike other synapses, gap junctions do not have a space or a gap separating one neuron from the next.
Instead, at gap junctions, the ion channels in the membrane of the presynaptic neuron make direct contact with the ion channels in the postsynaptic membrane. In addition, the ion channels on both the presynaptic and postsynaptic sides are always open. As a consequence, each time the presynaptic neuron depolarizes, the postsynaptic neuron will automatically depolarize as well. Typically, electrical synapses are found on neurons that need to work in synchrony, such as neurons that control breathing in the left and right nostrils, or neurons that control heart rate.