Neurotransmission

The fundamental role of a neuron is to receive, propagate, and transmit nerve signals. Its plasma membrane possesses specific electrochemical properties that allow it to react to a stimulus and propagate its action to the nerve ending.

The plasma membrane of neurons contains channels and pumps capable of regulating the distribution of ions on either side of the membrane according to their electrical charge and concentration. We will see that this regulation plays a primary role in the transmission of nerve impulses.

Unlike an electrical wire, it is not the flow of electrons that conducts the signal ^[96], but a wave of ionic exchanges occurring across the membrane. This propagation is therefore electrochemical in nature.

Fundamental Notions :

Two notions are very important to take into account: the concentration gradient ^[39] and the electrical gradient ^[39].

Indeed, in biological systems, molecules tend to diffuse from areas of high concentration toward areas of low concentration; they are then said to follow their concentration gradient.

Charged molecules also follow an electrical gradient (potential gradient); thus, positively charged molecules will diffuse toward negatively charged areas and vice versa.

However, these molecules are often shared between different, and sometimes even opposite, electrical and concentration gradients. They will then diffuse in a balanced manner according to these two gradients, following an electrochemical gradient ^[100].

The resting potential :

The diffusion of ions across the plasma membrane occurs through specific channels ^{[5, 75]}. Potassium channels are highly permeable ^[113], which is not the case for sodium channels. Indeed, at rest, the membrane is poorly permeable to sodium; it is even considered impermeable to it.

On the plasma membrane, there is a Na+-K+-ATPase pump that actively moves - with each consumption of an ATP molecule (the universal currency of cellular energy) - 3 sodium ions out of the cell for every 2 K+ ions moved inside. This pump consumes so much energy that some have attributed 30% or even 50% of all the energy consumed by the brain to it.

Overall, the Na+-K+-ATPase pump fills the cell with potassium and empties it of sodium; with each intervention, it moves a net positive charge toward the outside of the cell.

Intracellular K+ ions follow their chemical gradient and exit toward the extracellular milieu, bringing more and more positive charges with them. The intracellular side of the membrane thus becomes negatively charged, which limits the further diffusion of potassium ions.

Therefore, outside of any transmission, the equilibrium established by all these elements creates an electrical potential difference between the positively charged extracellular medium and the negatively charged intracellular medium. This transmembrane potential is called the resting potential, and it is often situated between -50 and -75 mV.

There are other molecules and other intervening elements that have not been detailed here to simplify the phenomenon; otherwise, it is much more complicated ^{[39, 41, 100, 133]}.

The action potential :

There is a voltage-gated sodium channel on the membrane that only opens during a variation in electrical potential between the two sides of the membrane ^{[39, 41]}. When the membrane potential exceeds a threshold value, the voltage-gated sodium channels open and cause a massive influx of Na+ ions into the cell (approximately 1 million/second ^{[96, 134]}) until the polarity of the membrane reverses (depolarization phase).

Potassium can then follow its concentration gradient and exit the cell; this gradually brings the membrane potential back to its resting state (repolarization phase). During this phase, sodium channels are inactivated and cannot be opened during a refractory period.

Sodium continues to be actively pumped out of the cell as potassium ions rejoin the interior.

The delay in potassium returning to the cell is responsible for a hyperpolarization that gradually regresses.

Signal propagation :

When membrane depolarization occurs for one reason or another - most often at the level of the axon hillock ^[113], where the concentration of voltage-gated sodium channels is most pronounced - nearby channels are activated, and so on.

This wave of depolarization continues until the membrane depolarization signal traverses the entire axonal length and ends at the terminal button.

The refractory period of voltage-gated sodium channels prevents the signal from moving backward ^[135]; thus, the signal always propagates in only one direction. This wave of action potentials is called the nerve impulse. The propagation of this impulse obeys the all-or-none law: either the transmembrane potential exceeds a threshold value and results in an action potential, or it is simply ignored.

On a single nerve fiber, the amplitude of the action potential does not vary; the encoding of signal intensity is determined by the frequency of the action potentials - the more action potentials there are, the more intense the signal.

The speed of nerve impulse transmission varies from one neuron to another. Indeed, the larger the diameter of the axon, the faster the signal propagates.

The speed of the nerve impulse also depends on the myelination of the axon ^[100]: in myelinated fibers, the action potential jumps from node to node; this is referred to as saltatory transmission, which is very fast (up to 120 m/s ^{[75, 119]}), as opposed to the continuous propagation in unmyelinated fibers, which is slower.

In myelinated fibers, Na+ channels are concentrated at the nodes; the action potential recorded at this level is so significant that it can rapidly influence the sodium channels in the next node, and so on.