Synapses - The Connection of Our Nerves

At the end of the neuron's axon, the action potential reaches the synapse.

The synapse (synaptic terminal) consists of the presynaptic membrane (at the end of the axon), the synaptic cleft (filled with extracellular fluid), and the postsynaptic membrane (e.g., dendrite, muscle cell).

It forms the contact point with another neuron (dendrite), a muscle cell, a gland cell, or an organ.

The synapse therefore represents a connection between two excitable cells. It converts electrical impulses (from the nerve cell) into a chemical messenger (neurotransmitter), which in turn triggers an electrical impulse, either inhibiting or depolarizing the postsynaptic cell!

Chemical synapse schema cropped, marked as public domain, details on Wikimedia Commons

Synapses – Electrical signal transmission, chemical transfer

The action potential is transmitted from the cell body via the axon, which, as we know, can be very long. The better insulated the axon is, the faster this stimulus transmission works—in fact, that is how it functions over long distances in the first place.

We have nerves with different thicknesses of myelin sheath and, consequently, different conduction velocities (better insulation means faster speeds). This has major benefits, as we will see later/in another blog post!

The electrical action potential triggers the release of neurotransmitters in the synapse in combination with Ca+, which are stored there packed in vesicles. These neurotransmitters diffuse through the synaptic cleft, where they in turn trigger an action—for example, a new depolarization of a nerve cell or a muscle cell (resulting in muscle contraction).

anonymous, Chem. Synapse scheme, marked as public domain, details on Wikimedia Commons

A neuron specializes in a specific function and therefore in specific neurotransmitters! This means it primarily uses one specific neurotransmitter to trigger an action. The neurotransmitters are specific to certain receptors, working like a lock-and-key system.

These neurotransmitters are divided into excitatory or inhibitory substances, where excitatory ones result in the transmission of the signal (e.g. acetylcholine in motor transmission), while inhibitory ones result in non-transmission, blocking and turning off the signal accordingly.

Inhibitory neurotransmitters act on the postsynaptic membrane only affecting the conductivity of K+ channels (see our action potential blog): Due to the K+ efflux (outflow from the cell interior), the already negative cell interior becomes even more negative and the membrane is hyperpolarized! This prevents any further immediate excitation by impulses! This is called an inhibitory postsynaptic potential (IPSP, with inhibition from -70 to -100mV). In this moment and state, the membrane is completely unresponsive to stimuli!

Savant-fou, Synapse neuro-neuronale, CC BY-SA 3.0

Neurotransmitter Production

Neurotransmitters like acetylcholine (the transmitter in motor transmission) are produced in the cell body (here from choline and acetyl). Acetyl is a substance produced in our mitochondria during the citric acid cycle—a cycle for energy production combined with oxygen. Thanks to this constant production, it is always abundantly available. Choline, however, is not available to the body in such large quantities.

The finished neurotransmitters are packed into granules or vesicles (small bubbles) and also transported along the axon to the synapses, where they are stored ready for release.

After being released into the synaptic cleft, the neurotransmitters are rapidly broken down back into their original building blocks by highly specific enzymes (e.g., acetylcholinesterase for acetylcholine). These breakdown products are either washed away with the bloodstream (such as acetyl) or reabsorbed into the synapse (such as choline, which is less common than acetyl). After being transported back to the nucleus, these are synthesized into new neurotransmitters once again.

A fast breakdown of the released and active neurotransmitters is essential: action potentials often arrive in rapid succession (1-2 ms, as we saw in our previous blog), and these signals must be passed on quickly.

On the other hand, a continuous action of acetylcholine on a muscle cell would result in a permanent, continuous contraction.

Diseases and Pathologies

It is also important to know that these neurotransmitters, like all substances, are produced by the nerve cell itself within its cell body. The entire axon is also supplied with its own vessels and pathways from the cell nucleus. But this also means that they have to be transported the long way from the cell body all the way to the synapse!

And that is exactly where the problem lies in various pathologies: For example, if there is pressure (from an intervertebral disc) on the cell body of a motor neuron located in the spinal cord, the production of these neurotransmitters is disrupted. This can lead to symptoms of paralysis.

If a structure puts pressure on the axon instead, its blood circulation (including the axonal transport of the transmitters packed in vesicles) is disrupted. This can lead to pain and paresthesia, or, under greater pressure, to motor deficits as well.

This explains why pressure on an axon may be highly painful, but is not always as dramatic as pressure directly on the cell nucleus: if the cell nucleus dies (which can happen in a relatively short time and is a medical emergency), the entire neuron is lost. However, as long as the necessary substances and building blocks can still be produced in the cell nucleus, there is a chance for regeneration and recovery of the neural structures.

Poisoning and the Effects of Toxins

Another issue is competitive inhibition by other substances: Competitive because there are molecules whose structure and shape fit the receptor even better (higher affinity) than the neurotransmitter itself! This substance has no active effect, but it occupies the receptor, preventing the transmitter from binding and therefore blocking any reaction from being triggered!

This happens, for example, in carbon monoxide (CO) poisoning (smoke inhalation): the gas binds to hemoglobin much better (higher affinity) than oxygen. This blocks oxygen transport through the blood, which can have fatal consequences.

This principle of competitive inhibition is also frequently utilized in insecticides, preventing neurotransmitters from binding.

Another mechanism is an inhibitory effect on acetylcholinesterase (the breakdown enzyme for acetylcholine), as seen with the nerve gas Sarin. This results in a continuous contraction of the muscles, which has fatal consequences due to its impact on our respiratory system.

Training and Rehabilitation

Synapses are incredibly adaptable: On one hand, more synapses can be built; on the other hand, more receptors can be integrated into the postsynaptic membrane. These represent two pathways or mechanisms for altering/sensitizing the signal, and receptors in particular can be integrated into a membrane relatively quickly.

Postsynaptic density, Katharina Heupel et al,Postsynaptic density, CC BY 2.0

Whenever you need us, we are here for you!

Your BodyLab Team – Your Connective Tissue Specialists

Osteopathy and Physiotherapy | Rehabilitation and Training

Zurich Altstetten

Cover Image Credits

Savant-fou, Synapse neuro-neuronale, CC BY-SA 3.0