Synapses
In 1897, the English neurophysiologist Charles Sherrington [74] observed that the speed of the nerve impulse from the cortex to the limbs was lower than that of its propagation within a single nerve fiber. He concluded that there must be some sort of interruption slowing down the transmission of the impulse. Thus, he introduced the concept of the synapse (from the Greek syn, meaning "together," and haptein, meaning "to touch" or "to grasp"; i.e., "connection") [52].
Indeed, neurons communicate with each other through synapses. A single neuron can have between 1,000 and 10,000 synapses [109] (approximately 300,000 on cerebellar Purkinje cells [57]). Multiply this number by 100 billion neurons to get an idea of the sheer number of communications within the nervous system!
Classification :
Synapses can be classified according to their location, structure, function, or the nature of the neurotransmitter released [39, 71].
According to location :
Axonal terminals can be in contact with dendrites (axodendritic synapse), the perikaryon (axosomatic synapse), or even end on another axon (axo-axonic synapse) [4].
According to their nature :
There are two main categories of synapses [41]:
Electrical synapses [42] , which form gap junctions between certain neurons; they play an important role during development and often transform into chemical synapses later. In adults, they are limited to a few regions of the brain.
Chemical synapses [52] are by far the most widespread; the signal travels via the secretion of chemical mediators called neurotransmitters or neuromediators. These neurotransmitters can have an excitatory effect (e.g., acetylcholine, glutamate) or an inhibitory effect (e.g., GABA). A neuron may secrete more than one type of neurotransmitter [38, 39, 41].
According to the postsynaptic cell:
Synapses can connect neurons with other neurons or with effector cells [2]: glandular (neuroglandular junction) or muscular (neuromuscular junction).
Anatomy of a synapse :
A synapse consists of three parts [5] : a presynaptic region, which corresponds to the terminal button of the presynaptic axon; a postsynaptic region (the area opposite the terminal button); and an intervening space called the synaptic cleft.
The terminal button contains synaptic vesicles filled with neurotransmitters and several mitochondria (an energy source). The postsynaptic part does not contain synaptic vesicles, which makes signal propagation unidirectional at this level.
The postsynaptic part contains receptors, most often of the channel-linked type, which open in response to the action of the released neurotransmitters.
Process :
When a train of action potentials (a succession of action potentials) arrives at the terminal button, it triggers the opening of voltage-gated calcium channels. Calcium then enters the cell massively and, through a cascade of chemical reactions [39, 57], stimulates the fusion of synaptic vesicles with the plasma membrane. On average, 300 synaptic vesicles are released with each action potential [57]. The greater the number of action potentials, the more vesicles are released.
The neurotransmitters diffuse toward the postsynaptic region to activate their receptors and are then rapidly eliminated [57], either by diffusion out of the synaptic cleft (where they are captured by gliocytes) or by degradation by a specific enzyme and reabsorbed by the terminal button to produce more neurotransmitters (reuptake [100]).
Post-Synaptic potentials :
Excitatory post-synaptic potential :
In an excitatory synapse, the neurotransmitter causes sodium channels to open, allowing sodium to enter the cell and creating a local depolarization called an Excitatory Post-Synaptic Potential (EPSP) [4, 39, 41].
This rarely triggers an action potential in the dendrites or perikaryon, as these two regions are very sparse in voltage-gated sodium channels. It is therefore a graded potential whose amplitude decreases over time and distance from the excitatory synapse to the axon hillock (an area extremely rich in voltage-gated sodium channels and the usual site of action potential initiation).
Inhibitory Post-Synaptic Potential :
In an inhibitory synapse, the neurotransmitter (e.g., GABA) causes the opening of chloride channels (allowing chloride to enter the cell) or potassium channels (allowing potassium to exit the cell) in the postsynaptic region.
In both cases, there is a local hyperpolarization of the plasma membrane called an Inhibitory Post-Synaptic Potential (IPSP) [4]. This hyperpolarization diffuses in the same way as the EPSP to the axon hillock, where it makes it more difficult to generate an action potential. Inhibitory synapses are often located near the axon hillock, where their inhibitory action can be most effective.
Integration :
In real time, it is rare for a single stimulation to generate an AP. The neuron receives multiple stimuli simultaneously. The processing of these stimuli occurs at the axon hillock through spatial and temporal summation of the various potentials received [38, 39, 54].
In spatial summation [1]: if the sum of excitatory and inhibitory potentials from different synapses arriving at the axon hillock at the same time exceeds a threshold value, it will trigger an action potential; otherwise, it will be ignored.
In temporal summation [52]: if many excitatory potentials occur close together in time, they add up and can also reach the depolarization threshold to trigger an action potential.
The axon hillock then acts as a neural integrator [96], deciding - based on the various potentials gathered - whether or not to trigger an action potential.