Synapse (from the Greek σύν syn 'together'; ἅπτειν haptein 'grasp, grasp, touch') describes the point of a neural link through which a nerve cell is in contact with another cell - a sensory cell, muscle cell, glandular cell or another nerve cell . Synapses are the transfer of excitement , but also allow the modulation of the signal transmission , and they are capable of addition by adaptive changes to store information. The number of synapses in the adult brain is around 100 trillion (10 14 ) - based on a single neuron, it varies between 1 and 200,000.
The term synapse was coined in 1897 by Charles S. Sherrington for the connection between neurons, for example between the branched end of the axon of one nerve cell and the branched dendrite of another nerve cell.
In most cases they are chemical synapses . With them, the signal that arrives as an electrical action potential is converted into a chemical signal, carried in this form across the synaptic gap between the cells , and then converted back into an electrical signal. The sending cell releases ( presynaptically ) messenger substances, neurotransmitters , which bind to the membrane receptors of the receiving cell on the other side of the gap ( postsynaptically ) . As a result, the direction of signal transmission (only forwards) is anatomically determined, which is fundamental for the processing of information in neural networks . The excitation- transmitting transmitter is either formed in the terminal of the axon of the sending neuron or is synthesized in its cell body and axonally transported to the presynaptic membrane regions.
In contrast, electrical synapses, as gap junctions, are contact points in which ion channels in two cells directly couple to one another and thus allow ions and small molecules to pass from one cell to the other. Such synapses between neurons were first discovered, but similar contact points can be found in other tissues, including plants.
In a figurative sense, immunological synapses are the sites of temporary cellular contacts between cells of the immune system, both with one another and with cells in the surrounding tissue. Molecules on the surface of one cell bind to receptor molecules and adhesion molecules in the cell membrane of the other and use them to exchange information.
|Construction of a chemical synapse|
In a synapse end button , the incoming action potential leads during the depolarization phase - in addition to the brief opening of sodium and somewhat delayed also of potassium ion channels - to the temporary opening of voltage-activated calcium ion channels and thus to a brief influx of calcium ions. The intracellularly increased calcium causes a messenger substance to be released into the synaptic gap within a few milliseconds. This neurotransmitter is kept in stock in special synaptic vesicles in the terminal button and made available in synaptic vesicles close to the cell membrane , which can fuse with the presynaptic membrane under the action of calcium and then release the transmitter molecules as they empty outwards.
This process, which is also called exocytosis , is only possible through the change in conformation of calcium-binding proteins, especially synaptotagmines . They trigger the formation of a protein complex from SNARE proteins - from a synaptobrevin in the vesicle membrane on the one hand and a syntaxin and two SNAP proteins in the cell membrane on the other hand - which allows both membranes to fuse. Other proteins are then involved in causing the fused vesicle to open extracellularly and, such as Complexin I and II, to accelerate the release of neurotransmitters. Then a certain number of synaptic vesicles are again provided on the axolemm via synapsin .
On the other side of the synaptic gap there are specific receptor molecules for the neurotransmitter in the postsynaptic , subsynaptic , membrane of the target cell. These receptors are mostly associated with ligand-gated ion channels ( ionotropic ), so that an ion channel can open immediately when the transmitter molecule binds to the appropriate receptor. Depending on the type of ion for which this channel is permeable, the membrane potential in the postsynaptic region is either increased ( EPSP ) or decreased ( IPSP ) by the ion current . Depending on the type of receptor , a so-called second messenger cascade can also be indirectly triggered ( metabotropic ), which can also lead to a change in the membrane potential and, under certain circumstances, also trigger further processes in the postsynaptic cell. Thus - mediated by the respective intracellular messenger substance - a signal amplification can also be caused, but only with a delayed effect.
The transmitter molecules do not bind irreversibly, but detach themselves from their receptor after a certain time. In the synaptic cleft or in the extracellular space , they are often broken down by special enzymes (such as acetylcholinesterase ) and thus their effect is limited. In the case of some transmitters, there is no degradation, but rather they are taken up again in the presynaptic terminal (e.g. serotonin ) or cleared away by glial cells .
The signals transmitted via chemical synapses have a biochemically defined effect. Depending on the features of the postsynaptic membrane on which the sending neuron influences, either an excitatory ( excitatory ) or an inhibitory ( inhibitory ) effect is achieved. Not only individual synapses, whole neurons are therefore differentiated into excitatory and inhibitory, depending on whether they only develop excitatory or only inhibitory synapses on target cells. For a target cell within the central nervous system, it is usually the case that it receives signals from different neurons, including opposing ones, and that the changes in electrical voltage that they trigger add up. If the sum of the incoming excitatory and inhibitory (postsynaptic) voltage changes on the axon hill of this nerve cell exceeds a certain threshold value for the change in potential, this cell becomes active in turn, forms an action potential and transmits it via its axon.
In the case of a large number of psychiatric and neurological diseases, it is assumed that synaptic transmission pathways are disrupted. There are indications of a connection between different forms of depression and disturbances in signal transmission by the neurotransmitter serotonin .
Numerous drugs or toxins develop their effect through an interaction with steps of the transmission to synapses ( beta blockers , nicotine , atropine , hyoscyamine , parathion , cocaine and many more).
The majority of synapses work with chemical information transmission, but in some cases there is also direct electrical transmission. In these electrical synapses, the action potential is passed on to the next cell directly and without mediating neurotransmitters.
In many electrical synapses, there are connecting channels through the cell membrane, called “ gap junctions ”, via which the intracellular spaces of cells that are directly adjacent to one another are coupled with one another. These gap junctions are pores in the cell membrane that are formed by certain proteins called connexins . Six connexin molecules line the pore of a cell, together they form a connexon . The contact between two connexons of neighboring cells then creates a channel that crosses the membranes and connects the two. The open connection allows diffusion of even medium-sized molecules, e.g. B. secondary messenger substances , and enables a very rapid transmission of changes in the membrane potential via ion passages with relatively low electrical resistance . Such electrical synapses occur, for example, between neurons in the retina; They are also found between glial cells and especially between cells of the heart muscle, which can act in a synchronized manner, electrically coupled to a common unit, similarly to smooth muscles such as the uterus.
Further classifications of synapses
Synapses can also be differentiated according to various aspects, for example
- after the cell linked to a nerve cell in
- according to the interneuronally connecting cell parts between neurons in
- Axo-dendritic synapses: axon endings that are in contact with a dendrite of the downstream neuron.
- Axo-somatic synapses: axons or collaterals that contact the cell body of a downstream nerve cell.
- Axo-axonic (also axo-axonal) synapses: axon of one neuron in contact with the neurite of another neuron.
- Dendro-dendritic synapses: couple the dendrites of the dendrite trees of different neurons with each other.
- Dendrosomatic synapses: link dendrites of one nerve cell to the body of another; so z. B. in the olfactory bulb .
- Somato-somatic synapses: connect the cell body of a neuron with that of an immediately adjacent neuron.
- Somato-dendritic synapses: between a nerve cell body and the dendrites of another nerve cell.
- Somato-axonal synapses: between the cell body of one and the axon of another nerve cell (e.g. in vegetative ganglia ).
- according to the manner of the composition of the linked cells in
- complex synapses involving more than two cells, connected in series or in parallel.
- synaptic glomeruli, mostly clusters of numerous interconnections enveloped by glia, convergent or divergent.
- reciprocal synapses, in which two synapses are next to each other, one to the other, exciting or inhibiting.
- according to the effect on the activity of the target cell in
- according to the material substance of the neurotransmitter in
Chemical synapses work with different transmitters and can be changed by medication or drugs in different steps of the signal transmission, whereby different effects can be achieved depending on the attack location and preconditions. However, differentiated functions of the nervous system cannot be influenced in a targeted manner, since these do not depend on the transmitter substance, but on the connection pattern of the synapses.
Chemical synapse toxins disrupt or prevent the function of synapses. They can block the release of the neurotransmitters into the synaptic gap or be so similar to the neurotransmitters that they bind to the receptor molecules in the postsynaptic membrane in their place and thus disrupt the transmission of excitation. Depending on the way in which it binds to the receptor, it can either occupy a single space or, in addition, achieve a similar effect as the actual transmitter. According to the effect achieved, substances with a similar activity are therefore referred to as agonists and differentiated from antagonists with the sole activity of inhibiting agonists in their effect - for example by taking their place.
The most well-known substances with a disruptive influence on synaptic transmission include numerous poisonous alkaloids from plants such as atropine , nicotine , mescaline , curare or from mushrooms such as those of ergot or muscarine . But drinking alcohol also influences the transmission to synapses, changing e.g. B. GABA receptors and blocked (NMDA) -glutamate receptors . A poison that is effective even in very small doses is botulinum toxin (botulin) formed by a type of bacterial clostridia - the paralyzing effect of which is used cosmetically to smooth out wrinkles - and the similar tetanus toxin . The neurotoxins produced by animals include, for example, the conotoxins of maritime cone snails and the poisons of various species of spiders, such as the latrotoxins of the thirteen-spotted black widow . Synthetic synapse poisons are the chemical warfare agents tabun , sarin and VX as well as numerous insecticides such as E 605 or neonicotinoids , as well as various hallucinogens such as LSD and others - and of course psychotropic drugs .
Changes in the synapse connections
The transferability of synapses is subject to anatomical change processes. These are the basics of learning and are described under Synaptic Plasticity .
- Susanne tom Dieck, Eckart D. Gundelfinger: Chemical synapses of the central nervous system . Chemistry in our time 34 (3), pp. 140-148 (2000),
- Elliot Valenstein : The War of the Soups and the Sparks: The Discovery of Neurotransmitters and the Dispute Over How Nerves Communicate. 2005, ISBN 0-231-13588-2 (book on the history of synapses research)
- Gerhard Neuweiler : The dynamic synapse . Naturwissenschaftliche Rundschau 59 (12), pp. 641-650 (2006),
- Electron microscopic images of synapses , University of Mainz
- Synapses Poison Summary , Document Online
- CS Sherrington: The integrative action of the nervous system. Yale University Press, New Haven 1906, p.18 .
- Karl-Josef Moll, Michaela Moll: Anatomie. 18th edition, Urban & Fischer, 2006, p. 123.
- F.-J. Kretz, K. Becke: Anesthesia and intensive care medicine in children. 2nd edition, Georg Thieme Verlag, 2006, ISBN 978-3-13-110232-4 , p. 23.