Synaptic Transmission

In my last post, I mentioned that action potentials can result in the release of neurotransmitters. One such cell that does this is the neuron. In this post, I will discuss how neurons secrete neurotransmitters into a synapse, which is a small space between two neurons.

Describe neurotransmitter & synaptic physiology

Essentially, the main idea behind neurotransmitters and synapses is this: an action potential reaches the end of the first neuron (a.k.a. the "presynaptic neuron"), stimulating the presynaptic neuron to release chemicals called neurotransmitters into the synaptic space (space between two neurons). The neurotransmitters then bind to receptors on the dendrites of the next neuron (a.k.a. the "postsynaptic neuron"), which could have an excitatory or inhibitory effect on the postsynaptic neuron.

Also, I just wanted to leave a quick note that some neurons are also able to transmit impulses through direct electrical transmission, without requiring a synapse. This is pretty rare, but it does happen.

List common neurotransmitters, their receptors and effects

Glutamate

Glutamate is the most common excitatory neurotransmitter in the central nervous system (CNS). It opens both iGluRs (ionotropic glutamate receptors) and mGluRs (metabotropic glutamate receptors). (Ionotropic is basically a fancy word for ion channel, and metabotropic is a fancy word for a receptor that activates an enzyme or is otherwise more interesting than an ion channel.) Two iGluRs that you might need to know are the AMPA receptor, which is a sodium channel, and the NMDA receptor, which is a sodium and calcium channel. Both of these receptors have excitatory effects, as allowing sodium and calcium into the cell makes it more positive and more likely to generate an action potential.

GABA (gamma-aminobutyric acid)

GABA is the most common inhibitory neurotransmitter in the central nervous system. Its receptors include GABA_ARs, which are ionotropic, and GABA_BRs, which are metabotropic. The ionotropic GABA_ARs are chloride channels, so they let negatively-charged chloride into the cell down its concentration gradient. As chloride makes the inside of the cell more negative (hyperpolarised), it has an inhibitory effect.

ACh (acetylcholine)

Acetylcholine is a common neurotransmitter in the peripheral nervous system. It binds to both nicotinic (nAChR) and muscarinic (mAChR) receptors. Nicotinic receptors are ionotropic sodium channels, and since they are letting in a positive ion, they are always excitatory. Muscarinic receptors are metabotropic and are usually inhibitory, but can be excitatory, depending on the pathway that they activate.

NA (noradrenaline / norepinephrine)

Noradrenaline is another common neurotransmitter in the peripheral nervous system. It binds to both alpha- and beta-adrenergic receptors. Both alpha- and beta-adrenergic receptors are metabotropic and can be excitatory or inhibitory, depending on the pathway that they activate.

Describe the processes involved in the regulated release of neurotransmitters

Most neurotransmitters are released via regulated exocytosis, as described here. The vesicles containing the neurotransmitters are coated with v-SNAREs called synaptobrevin, and these bind to t-SNAREs called SNAP on the inside of the neuron membrane. Prior to neurotransmitter release, synaptobrevin and SNAP can only partially assemble, as there is another protein called complexin that is in the way. In order to allow synaptobrevin and SNAP to assemble, yet another protein, called synaptotagmin, needs to help out. It is activation of synaptotagmin which is regulated, allowing the whole process of neurotransmitter release to be regulated.

Synaptotagmin is regulated by calcium entry into the terminal of the axon, as synaptotagmin needs to bind to calcium in order to become activated. When the action potential reaches the axon terminal, voltage-gated calcium channels open, allowing calcium to enter the cell and bind to synaptotagmin. Synaptotagmin helps to move complexin out of the way, allowing synaptobrevin and SNAP to bind, which in turn allows the vesicle to fuse with the membrane and secrete its neurotransmitters out into the syanpse.

Outline the metabolism (production and destruction) of neurotransmitters

Different neurotransmitters are produced and degraded differently. Many neurotransmitters are produced from amino acids. For instance, glutamate is an amino acid (glutamic acid), and it can be converted into GABA via glutamate decarboxylase. Nitric oxide, which is another neurotransmitter, can be produced from the breakdown of arginine. Dopamine, adrenaline, and noradrenaline, as well as thyroid hormone (not a neurotransmitter, but thought I'd include it for completeness), are all derived from tyrosine. Serotonin is derived from tryptophan.

Of course, after sending a neurotransmitter into the synapse, it is important that you can get rid of it eventually, or the signal would continue to affect the post-synaptic neuron until you die. There are two main ways in which a neurotransmitter can be removed from the synapse: re-uptake and degradation. In re-uptake, either the presynaptic neuron or the glial cells take up the neurotransmitter via various transporters. In degradation, various enzymes in the synapse break down the neurotransmitter. For instance, acetylcholinesterase breaks down acetylcholine into acetate and choline.

Describe the formation of both IPSPs and EPSPs

As mentioned earlier, various neurotransmitters can have excitatory or inhibitory effects by binding to various receptors on the postganglionic neuron. Remember, however, that neurons are receiving input from many different neurons at once. So, how does the neuron know whether to fire an impulse or not?

The answer lies in IPSPs (inhibitory post-synaptic potentials) and EPSPs (excitatory post-synaptic potentials). Unlike action potentials, IPSPs and EPSPs are not all-or-nothing: they are graded. Each IPSP or EPSP affects the postsynaptic neuron in a small way. It is the sum of the IPSPs and EPSPs that is crucial. If the IPSPs and/or EPSPs sum in such a way that the membrane potential is brought over the threshold potential, the postsynaptic neuron will fire an action potential.