 In this video I will describe the mechanism of neurotransmission at a chemical synapse, including the release of neurotransmitters and activation of postsynaptic receptors, contrast ionotropic receptors and metapotropic receptors, and categorized neurotransmitters by function. When the action potential reaches the axon terminal, voltage-gated calcium ion channels are stimulated to open, then calcium will rush from the extracellular fluid into the cytosol. Calcium will then bind to calcium sensor proteins that will stimulate synaptic vesicles to merge with the plasma membrane at the axon terminal in the mechanism of exocytosis. The synaptic vesicles will release neurotransmitters into the synaptic cleft. Then these neurotransmitters diffuse across the synaptic cleft and bind to receptors that are on the postsynaptic cell's plasma membrane. These neurotransmitter receptors can be ligand-gated ion channels that will cause greater potentials in the postsynaptic cell. If neurotransmitters were constantly present in the synaptic cleft binding to the receptors, we wouldn't be able to have information transmitted across the chemical synapse. Therefore, the neurotransmitters must be broken down or removed from the synapse. One of those mechanisms of removing a neurotransmitter from the synapse is reuptake by the presynaptic neuron where a transporter protein can pump the neurotransmitters back into the axon terminal of the presynaptic neuron. Another mechanism that will remove the neurotransmitters from the synaptic cleft is an enzymatic degradation. If there's an enzyme present in the synaptic cleft that can break down the neurotransmitter, this will also remove the signal. The last way for a neurotransmitter to be removed from the synapse is just by diffusion as it spreads away from the synapse. Ionotropic receptors are receptors for neurotransmitters that function as ion channels. These are also known as ion channel linked receptors or ligand-gated ion channels. The ligand is the neurotransmitter that binds to the receptor and this will activate a change in the shape of the receptor that opens a gate in the ion channel allowing ions to move across the plasma membrane. A metapotropic receptor, also known as a G-protein linked receptor, is a type of neurotransmitter receptor that when the neurotransmitter binds to the receptor, it will stimulate a metabolic change inside of the postsynaptic cell, producing an intracellular signal such as a second messenger molecule. For example, cyclic AMP can be produced as a second messenger in response to activation of a metapotropic neurotransmitter receptor. While ionotropic neurotransmitter receptors will always directly produce a graded potential, either an EPSP if the ion channel is a sodium ion channel or an IPSP if the ion channel is a chloride channel or a potassium channel. A metapotropic receptor can indirectly influence the production of graded potentials but does not directly produce any graded potentials. So a metapotropic receptor could produce an intracellular signal that then regulates the activity of an ion channel in order to produce EPSPs or IPSPs. Here are a few examples of major neurotransmitters that function in the human body. So acetylcholine is one of the major neurotransmitters that's released by neurons in the peripheral nervous system. We'll see acetylcholine is the neurotransmitter that stimulates the excitation of skeletal muscles but acetylcholine will also be an important neurotransmitter in the brain. And so acetylcholine can either be excitatory or inhibitory depending upon the context. Glutamate is one of the 20 amino acids that is used to synthesize proteins but glutamate is also used as a neurotransmitter. Glutamatergic neurons are the neurons that release glutamate and glutamate is the primary excitatory neurotransmitter in the central nervous system. So there's a very large number of neurons that use glutamate as their neurotransmitter and glutamate will function to stimulate EPSPs in the postsynaptic cell. Gabba or gamma amino butyric acid is another neurotransmitter that's a amino acid or modified from an amino acid and gabba is the primary inhibitory neurotransmitter in the central nervous system. So there's also a very large number of neurons that release the neurotransmitter, gabba and gabba will stimulate EPSPs in the postsynaptic cell. On the right here we see a few more examples of neurotransmitters that are modified from amino acids, norepinephrine is made from the amino acid tyrosine and we will see that norepinephrine is a major neurotransmitter in the peripheral nervous system. We'll see the sympathetic division of the autonomic nervous system will contain a large number of neurons that release the neurotransmitter norepinephrine. These are known as noreadrenergic neurons that release norepinephrine as we'll also see norepinephrine can function in the central nervous system and it will have a variety of functions depending on context. Dopamine is another neurotransmitter made from the amino acid tyrosine and we'll see that dopamine is an important neuromodulator, a neurotransmitter produced in the central nervous system that can fine-tune the response of other neurons so it can have an influence on the activity of other neurons that are responding in the central nervous system. Primarily we'll see this in the context of regulating motor commands in order to stimulate motivation for motor commands. Dopamine will be a neurotransmitter produced by neurons found in the brain's stem that will be released into another region of the brain known as the striatum, a basal nucleus region of the cerebrum and dopamine will help stimulate motivation helping to increase the likelihood that a motor command will be sent out from the brain to activate a skeletal muscle. Serotonin is another example, the last example of an amino acid-based neurotransmitter we see here so serotonin is produced from the amino acid tryptophan and serotonin has an important function in the central nervous system where it will be an important modulator of the activity of other neurons and will have an influence on our mood. We've learned the profound influence of serotonin on our mood as a result of discovering medications that are used to treat depression known as selective serotonin reuptake inhibitors. These drugs will inhibit the serotonin reuptake transporters increasing the concentration of serotonin in the synapse which has an effect of increasing a positive mood making people feel happier or it's an effective treatment for depression. Neurotransmitters can be functionally classified into two broad categories excitatory and inhibitory. Glutamate is the most common excitatory neurotransmitter in the central nervous system and so we'll use glutamate as an example of an excitatory neurotransmitter. An excitatory neurotransmitter like glutamate will stimulate an EPSP in the postsynaptic cell. The glutamate receptors are ligand gated sodium ion channels that will produce EPSPs as the sodium channel opens enabling sodium to enter the cell. GABA is an example of an inhibitory neurotransmitter. GABA is the primary inhibitory neurotransmitter in the central nervous system. An inhibitory neurotransmitter will stimulate an IPSP in the postsynaptic cell. The GABA receptors are ligand gated chloride ion channels as GABA binds to the GABA receptor opening the chloride ion channel. Chloride will enter the cell creating an IPSP while glutamate is an example of excitatory neurotransmitter in the central nervous system and GABA is an example of an inhibitory neurotransmitter in the central nervous system. We will see that some neurotransmitters can function as excitatory in one context and inhibitory in a different context. For example, the neurotransmitter acetylcholine will have excitatory functions such as stimulating skeletal muscle contraction and inhibitory functions such as inhibiting cardiac muscle decreasing the heart rate.