Synapses - The Connection of Our Nerves

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

The synapse (terminal button) 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 or gland cell, or an organ.

Thus, the synapse represents a connection between two excitable cells. It converts electrical stimuli (from the nerve cell) into a chemical messenger (neurotransmitter), which in turn triggers an electrical stimulus, 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 along the axon, which as we know can be very long. The better insulated the axon is, the faster this stimulus transmission works—and indeed, that is how it functions over long distances in the first place.

We have nerves with myelin sheaths of varying thickness, resulting in different conduction velocities (better insulated means faster). This offers great advantages, as we will explore 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 ready in vesicles. These neurotransmitters diffuse through the synaptic cleft, where they trigger another action, such as a new depolarization of a nerve cell or a muscle cell (followed by muscle contraction).

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

A neuron specializes in a specific function and thus in specific neurotransmitters! Therefore, it primarily has one specific neurotransmitter that can trigger an action. Neurotransmitters are specific to certain receptors, functioning like a lock-and-key mechanism.

These neurotransmitters are divided into excitatory or inhibitory substances. Excitatory substances result in the transmission of the signal (e.g., acetylcholine in motor transmission), while inhibitory substances prevent transmission, effectively blocking and shutting down the signal.

Inhibitory neurotransmitters act on the postsynaptic membrane solely by affecting the conductivity of K+ channels (see our action potential blog): due to K+ efflux (outflow from the cell interior), the already negative cell interior becomes even more negative, hyperpolarizing the membrane! Consequently, no further immediate excitation via impulses is possible! This is referred to as an Inhibitory Postsynaptic Potential (IPSP, with inhibition shifting from -70 to -100mV). In this moment and state, the membrane cannot be stimulated!

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 generating energy in combination with oxygen. Because of this constant production, it is abundantly available. Choline, however, is not available to the body in such large quantities.

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

After release into the synaptic cleft, neurotransmitters are rapidly broken down back into their original building blocks by specific enzymes (e.g., acetylcholinesterase for acetylcholine). The breakdown products are either washed away with the bloodstream (e.g., acetyl) or reabsorbed into the synapse (like choline, which is not as common as acetyl). After being transported back to the nucleus, these building blocks are synthesized into new neurotransmitters once again.

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

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

Diseases and Pathologies

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

This is precisely where the issue lies in various pathologies: if, for example, pressure (from a herniated disc) is exerted 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 presses on the axon instead, its blood supply (including the axonal transport of the transmitter vesicles) is disrupted. This can cause pain and paresthesia, or, with greater pressure, motor deficits as well.

This helps us understand why pressure on an axon may be highly painful, but not always as dramatic as pressure directly on the cell nucleus: if the cell nucleus dies (which can happen relatively quickly and constitutes 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 always a chance for regeneration and recovery of the neural structures.

Poisoning and the Effects of Toxins

Another challenge is competitive inhibition by other substances: competitive because there are molecules that, in terms of structure and shape, fit the receptor even better (higher affinity) than the neurotransmitter! However, this substance has no effect, but it blocks the receptor so the transmitter cannot dock, and consequently, no reaction is triggered!

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

This principle of competitive inhibition is also frequently utilized in insecticides to prevent neurotransmitters from docking.

Another mechanism is an inhibitory effect on acetylcholinesterase (the breakdown enzyme for acetylcholine), as seen with the nerve agent 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 highly adaptable: on one hand, more synapses can be built, and on the other hand, more receptors can be integrated into the postsynaptic membrane. These represent two powerful mechanisms for modifying / 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

If you need us, we are always here for you!

Your BodyLab Team, your connective tissue specialists

Osteopathy and Physiotherapy | Rehabilitation and Training

Zurich Altstetten

Cover Image Credit

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