The synaptic cleft represents the gap between two nerve cells within a chemical synapse. The electrical nerve signal from the first cell transforms into a biochemical signal at the terminal node and transforms back into an electrical action potential in the second nerve cell. Agents such as drugs, medications, and toxins can interfere with the function of the synapse, thereby affecting information processing and transmission within the nervous system.
What is the synaptic cleft?
Neurons transmit information in the form of electrical signals. At the junction between two neurons, the electrical signal must cross a gap. The nervous system has two ways to bridge this distance: electrical synapses and chemical synapses. The gap of the chemical synapse corresponds to the synaptic cleft. In humans, most synapses are chemical in nature. Electrical synapses are also known as gap junctions or nexuses; the term “synaptic cleft” is not commonly used for electrical synapses. Instead, neurology generally speaks of the extracellular space. In the nexus, the connection between neurons is formed by channels that grow from both the presynaptic cytoplasm and the postsynaptic cytoplasm and meet in the middle. Through these channels, electrically charged particles (ions) can move directly from one neuron to another.
Anatomy and structure
The synaptic cleft is 20 to 40 nanometers wide and thus can connect distances between two neurons that would be too far for gap junctions. On average, gap junctions bridge a distance of only 3.5 nanometers. The height of the synaptic cleft is about 0.5 nanometers. On one side of the gap is the presynaptic membrane, which corresponds to the cell membrane of the terminal knob. The terminal knob, in turn, forms the end of a nerve fiber, which thickens at this point, creating more space inside it. The cell needs this extra space for synaptic vesicles: membrane-encased containers that hold the cell’s messenger substances (neurotransmitters). On the other side of the synaptic cleft is the postsynaptic membrane. It belongs to the downstream neuron, which receives the incoming stimulus and transmits it under certain conditions. The postsynaptic membrane contains receptors, ion channels and ion pumps that are essential for the function of the synapse. Various molecules can move freely in the synaptic cleft, including neurotransmitters from the terminal bud of the presynaptic neuron, as well as enzymes and other biomolecules, some of which interact with the neurotransmitters.
Function and Tasks
Both the peripheral and central nervous systems transport information within a cell using electrical impulses. These action potentials originate at the axon hillock of the nerve cell and travel along the axon, which, along with its insulating myelin layer, is also known as the nerve fiber. At the terminal knob, located at the end of the nerve fiber, the electrical action potential triggers the influx of calcium ions into the terminal knob. They cross the membrane with the help of ion channels and cause a charge shift. As a result, some of the synaptic vesicles fuse with the outer membrane of the presynaptic cell, allowing the neurotransmitters they contain to enter the synaptic cleft. This crossing takes an average of 0.1 milliseconds. The neurotransmitters cross the synaptic cleft and can activate receptors at the postsynaptic membrane, each of which responds specifically to certain neurotransmitters. If the activation is successful, channels open in the postsynaptic membrane and sodium ions flow into the interior of the neuron. The positively charged particles change the electrical voltage state of the cell, which is slightly negative in the resting state. The more sodium ions flow in, the greater the depolarization of the neuron, i.e., the negative charge decreases. If this membrane potential exceeds the threshold potential of the postsynaptic neuron, a new action potential is generated at the axon hillock of the neuron, which again propagates in electrical form along the nerve fiber.To prevent the released neurotransmitters from permanently irritating the postsynaptic receptors and thus triggering permanent excitation of the nerve cell, there are enzymes in the synaptic cleft. They deactivate the neurotransmitters in the synaptic cleft, for example, by splitting them into their components. Following stimulation, ion pumps actively restore the initial state by exchanging particles at both the presynaptic and postsynaptic membranes.
Diseases
Numerous drugs, medications, and toxins that have an effect on the nervous system exert their effects at the synaptic cleft. An example of such a drug is monoamine oxidase (MAO) inhibitors, which are considered for the treatment of depression. Depression is a mental illness whose core features are depressed mood and loss of pleasure and interest in (almost) everything. Depression is caused by numerous factors and drug therapy is usually only part of the treatment. One influencing factor is disorders related to the neurotransmitters serotonin and dopamine. MAO inhibitors act by inhibiting the enzyme monoamide oxidase. This is responsible for the degradation of various neurotransmitters in the synaptic cleft; its inhibition accordingly means that neurotransmitters such as dopamine, serotonin and norepinephrine can continue to irritate the receptors of the postsynaptic membrane. In this way, even reduced amounts of the neurotransmitters can result in a sufficient signal. A different mechanism of action underlies nicotine. In the synaptic cleft, it irritates nicotinic acetylcholine receptors and thus causes the influx of ions into the postsynaptic cell, as does the main transmitter, acetylcholine.
