Chemical synapse

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This article is about chemical synapses of the nervous system. For general information, see synapse. For other uses, see synapse (disambiguation).
Artistic interpretation of the major elements in chemical synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the action potential reaches the presynaptic terminal, it provokes the release of a synaptic vesicle, secreting its quanta of neurotransmitter molecules. The neurotransmitter binds to chemical receptor molecules located in the membrane of another neuron, the postsynaptic neuron, on the opposite side of the synaptic cleft.

Chemical synapses are biological junctions through which

circuits within the central nervous system. They are crucial to the biological computations that underlie perception and thought. They allow the nervous system
to connect to and control other systems of the body.

At a chemical synapse, one neuron releases

neuroglia
to terminate the action of the neurotransmitter.

The adult human brain is estimated to contain from 1014 to 5 × 1014 (100–500 trillion) synapses.[1] Every cubic millimeter of cerebral cortex contains roughly a billion (short scale, i.e. 109) of them.[2] The number of synapses in the human cerebral cortex has separately been estimated at 0.15 quadrillion (150 trillion)[3]

The word "synapse" was introduced by Sir Charles Scott Sherrington in 1897.[4] Chemical synapses are not the only type of biological synapse: electrical and immunological synapses also exist. Without a qualifier, however, "synapse" commonly refers to chemical synapses.

Structure

Diagram of a chemical synaptic connection
Further information on formation of synapses: Synaptogenesis

Synapses are functional connections between neurons, or between neurons and other types of cells.

light microscope except as points where the membranes of two cells appear to touch, but their cellular elements can be visualized clearly using an electron microscope
.

Chemical synapses pass information directionally from a presynaptic cell to a postsynaptic cell and are therefore asymmetric in structure and function. The presynaptic

plasma membrane at regions called active zones
.

Immediately opposite is a region of the postsynaptic cell containing neurotransmitter receptors; for synapses between two neurons the postsynaptic region may be found on the dendrites or cell body. Immediately behind the postsynaptic membrane is an elaborate complex of interlinked proteins called the postsynaptic density (PSD).

Proteins in the PSD are involved in anchoring and trafficking neurotransmitter receptors and modulating the activity of these receptors. The receptors and PSDs are often found in specialized protrusions from the main dendritic shaft called dendritic spines.

Synapses may be described as symmetric or asymmetric. When examined under an electron microscope, asymmetric synapses are characterized by rounded vesicles in the presynaptic cell, and a prominent postsynaptic density. Asymmetric synapses are typically excitatory. Symmetric synapses in contrast have flattened or elongated vesicles, and do not contain a prominent postsynaptic density. Symmetric synapses are typically inhibitory.

The synaptic cleft—also called synaptic gap—is a gap between the pre- and postsynaptic cells that is about 20 nm (0.02 μ) wide.[12] The small volume of the cleft allows neurotransmitter concentration to be raised and lowered rapidly.[13]

An autapse is a chemical (or electrical) synapse formed when the axon of one neuron synapses with its own dendrites.

Signaling in chemical synapses

Overview

Here is a summary of the sequence of events that take place in synaptic transmission from a presynaptic neuron to a postsynaptic cell. Each step is explained in more detail below. Note that with the exception of the final step, the entire process may run only a few hundred microseconds, in the fastest synapses.[14]

  1. The process begins with a wave of electrochemical excitation called an action potential traveling along the membrane of the presynaptic cell, until it reaches the synapse.
  2. The electrical depolarization of the membrane at the synapse causes channels to open that are permeable to calcium ions.
  3. Calcium ions flow through the presynaptic membrane, rapidly increasing the calcium concentration in the interior.
  4. The high calcium concentration activates a set of calcium-sensitive proteins attached to vesicles that contain a neurotransmitter chemical.
  5. These proteins change shape, causing the membranes of some "docked" vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter contents into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells.
  6. The neurotransmitter diffuses within the cleft. Some of it escapes, but some of it binds to
    chemical receptor
    molecules located on the membrane of the postsynaptic cell.
  7. The binding of neurotransmitter causes the receptor molecule to be activated in some way. Several types of activation are possible, as described in more detail below. In any case, this is the key step by which the synaptic process affects the behavior of the postsynaptic cell.
  8. Due to thermal vibration, the motion of atoms, vibrating about their equilibrium positions in a crystalline solid, neurotransmitter molecules eventually break loose from the receptors and drift away.
  9. The neurotransmitter is either reabsorbed by the presynaptic cell, and then repackaged for future release, or else it is broken down metabolically.

Neurotransmitter release

Release of neurotransmitter occurs at the end of axonal branches.

The release of a neurotransmitter is triggered by the arrival of a nerve impulse (or

recycled
for the formation of fresh neurotransmitter-filled vesicles.

An exception to the general trend of neurotransmitter release by vesicular fusion is found in the type II receptor cells of mammalian taste buds. Here the neurotransmitter ATP is released directly from the cytoplasm into the synaptic cleft via voltage gated channels.[18]

Receptor binding

Receptors on the opposite side of the synaptic gap bind neurotransmitter molecules. Receptors can respond in either of two general ways. First, the receptors may directly open

transmembrane potential.[14] The resulting change in voltage is called a postsynaptic potential. In general, the result is excitatory in the case of depolarizing currents, and inhibitory in the case of hyperpolarizing currents. Whether a synapse is excitatory or inhibitory depends on what type(s) of ion channel conduct the postsynaptic current(s), which in turn is a function of the type of receptors and neurotransmitter employed at the synapse. The second way a receptor can affect membrane potential is by modulating the production of chemical messengers inside the postsynaptic neuron. These second messengers can then amplify the inhibitory or excitatory response to neurotransmitters.[14]

Termination

After a neurotransmitter molecule binds to a receptor molecule, it must be removed to allow for the postsynaptic membrane to continue to relay subsequent

IPSPs
. This removal can happen through one or more processes:

Synaptic strength

The strength of a synapse has been defined by Bernard Katz as the product of (presynaptic) release probability pr, quantal size q (the postsynaptic response to the release of a single neurotransmitter vesicle, a 'quantum'), and n, the number of release sites. "Unitary connection" usually refers to an unknown number of individual synapses connecting a presynaptic neuron to a postsynaptic neuron. The amplitude of postsynaptic potentials (PSPs) can be as low as 0.4 mV to as high as 20 mV.

neuromodulators or can change as a result of previous activity. Changes in the synaptic strength can be short-term, lasting seconds to minutes, or long-term (long-term potentiation, or LTP), lasting hours. Learning and memory are believed to result from long-term changes in synaptic strength, via a mechanism known as synaptic plasticity
.

Receptor desensitization

Desensitization of the postsynaptic receptors is a decrease in response to the same neurotransmitter stimulus. It means that the strength of a synapse may in effect diminish as a train of action potentials arrive in rapid succession – a phenomenon that gives rise to the so-called frequency dependence of synapses. The nervous system exploits this property for computational purposes, and can tune its synapses through such means as phosphorylation of the proteins involved.

Synaptic plasticity

Main article: Synaptic plasticity

Synaptic transmission can be changed by previous activity. These changes are called synaptic plasticity and may result in either a decrease in the efficacy of the synapse, called depression, or an increase in efficacy, called potentiation. These changes can either be long-term or short-term. Forms of short-term plasticity include synaptic fatigue or depression and synaptic augmentation. Forms of long-term plasticity include long-term depression and long-term potentiation. Synaptic plasticity can be either homosynaptic (occurring at a single synapse) or heterosynaptic (occurring at multiple synapses).

Homosynaptic plasticity

Main article: Homosynaptic plasticity

Homosynaptic plasticity (or also homotropic modulation) is a change in the synaptic strength that results from the history of activity at a particular synapse. This can result from changes in presynaptic calcium as well as feedback onto presynaptic receptors, i.e. a form of autocrine signaling. Homosynaptic plasticity can affect the number and replenishment rate of vesicles or it can affect the relationship between calcium and vesicle release. Homosynaptic plasticity can also be postsynaptic in nature. It can result in either an increase or decrease in synaptic strength.

One example is neurons of the

α2-adrenergic receptors, inhibiting further release of noradrenaline.[21] This effect is utilized with clonidine
to perform inhibitory effects on the SNS.

Heterosynaptic plasticity

Main article: Heterosynaptic plasticity

Heterosynaptic plasticity (or also heterotropic modulation) is a change in synaptic strength that results from the activity of other neurons. Again, the plasticity can alter the number of vesicles or their replenishment rate or the relationship between calcium and vesicle release. Additionally, it could directly affect calcium influx. Heterosynaptic plasticity can also be postsynaptic in nature, affecting receptor sensitivity.

One example is again neurons of the

noradrenaline, which, in addition, generates an inhibitory effect on presynaptic terminals of neurons of the parasympathetic nervous system.[21]

Integration of synaptic inputs

Main article: Summation (neurophysiology)

In general, if an excitatory synapse is strong enough, an action potential in the presynaptic neuron will trigger an action potential in the postsynaptic cell. In many cases the excitatory postsynaptic potential (EPSP) will not reach the threshold for eliciting an action potential. When action potentials from multiple presynaptic neurons fire simultaneously, or if a single presynaptic neuron fires at a high enough frequency, the EPSPs can overlap and summate. If enough EPSPs overlap, the summated EPSP can reach the threshold for initiating an action potential. This process is known as summation, and can serve as a high pass filter for neurons.[22]

On the other hand, a presynaptic neuron releasing an inhibitory neurotransmitter, such as

Nobel Prize for Physiology or Medicine
in 1963.

Volume transmission

When a neurotransmitter is released at a synapse, it reaches its highest concentration inside the narrow space of the synaptic cleft, but some of it is certain to diffuse away before being reabsorbed or broken down. If it diffuses away, it has the potential to activate receptors that are located either at other synapses or on the membrane away from any synapse. The extrasynaptic activity of a neurotransmitter is known as volume transmission.[23] It is well established that such effects occur to some degree, but their functional importance has long been a matter of controversy.[24]

Recent work indicates that volume transmission may be the predominant mode of interaction for some special types of neurons. In the mammalian cerebral cortex, a class of neurons called

neurogliaform cells can inhibit other nearby cortical neurons by releasing the neurotransmitter GABA into the extracellular space.[25] Along the same vein, GABA released from neurogliaform cells into the extracellular space also acts on surrounding astrocytes, assigning a role for volume transmission in the control of ionic and neurotransmitter homeostasis.[26] Approximately 78% of neurogliaform cell boutons do not form classical synapses. This may be the first definitive example of neurons communicating chemically where classical synapses are not present.[25]

Relationship to electrical synapses

An

Mauthner cells.[32]

Effects of drugs

Main article: Neuropharmacology

One of the most important features of chemical synapses is that they are the site of action for the majority of

GABA. LSD interferes with synapses that use the neurotransmitter serotonin. Cocaine blocks reuptake of dopamine
and therefore increases its effects.

History and etymology

During the 1950s, Bernard Katz and Paul Fatt observed spontaneous miniature synaptic currents at the frog neuromuscular junction.[33] Based on these observations, they developed the 'quantal hypothesis' that is the basis for our current understanding of neurotransmitter release as exocytosis and for which Katz received the Nobel Prize in Physiology or Medicine in 1970.[34] In the late 1960s, Ricardo Miledi and Katz advanced the hypothesis that depolarization-induced influx of calcium ions triggers exocytosis.

Sir Charles Scott Sherringtonin coined the word 'synapse' and the history of the word was given by Sherrington in a letter he wrote to John Fulton:

'I felt the need of some name to call the junction between nerve-cell and nerve-cell... I suggested using "syndesm"... He [ Sir Michael Foster ] consulted his Trinity friend Verrall, the Euripidean scholar, about it, and Verrall suggested "synapse" (from the Greek "clasp").'–Charles Scott Sherrington[4]

See also

Notes

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  2. PMID 18779570
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  3. ^ Brain Facts and Figures Washington University.
  4. ^
    ISBN 9780801871184
    . Retrieved 9 June 2020.
  5. ^ Rapport, Richard L. (2005). Nerve Endings: The Discovery of the Synapse. W. W. Norton & Company. pp. 1–37.
    ISBN 978-0-393-06019-5
    .
  6. ^ Squire, Larry R.; Floyd Bloom; Nicholas Spitzer (2008). Fundamental Neuroscience. Academic Press. pp. 425–6.
    ISBN 978-0-12-374019-9
    .
  7. ^ Hyman, Steven E.; Eric Jonathan Nestler (1993). The Molecular Foundations of Psychiatry. American Psychiatric Pub. pp. 425–6.
    ISBN 978-0-88048-353-7
    .
  8. ^ Smilkstein, Rita (2003). We're Born to Learn: Using the Brain's Natural Learning Process to Create Today's Curriculum. Corwin Press. p. 56.
    ISBN 978-0-7619-4642-7
    .
  9. ^
    ISBN 978-0-387-95526-1
    . Axons connecting dendrite to dendrite are dendrodendritic synapses. Axons which connect axon to dendrite are called axodendritic synapses
  10. ^ a b Garber, Steven D. (2002). Biology: A Self-Teaching Guide. John Wiley and Sons. p. 175.
    ISBN 978-0-471-22330-6
    . synapses connect axons to cell body.
  11. ^ a b Weiss, Mirin; Dr Steven M. Mirin; Dr Roxanne Bartel (1994). Cocaine. American Psychiatric Pub. p. 52.
    ISBN 978-1-58562-138-5
    . Retrieved 2008-12-26.     Axons terminating on the postsynaptic cell body are axosomatic synapses. Axons that terminate on axons are axoaxonic synapses
  12. S2CID 125516633
    .
  13. ^ a b Kandel, Schwartz & Jessell 2000, p. 182
  14. ^ a b c Bear, Mark F; Connors, Barry W; Paradiso, Michael A (2007). Neuroscience: exploring the brain. Philadelphia, PA: Lippincott Williams & Wilkins. pp. 113–118.
  15. ^ Llinás R, Steinberg IZ, Walton K (1981). "Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse". Biophysical Journal. 33 (3): 323–351.
    PMID 6261850
    .
  16. S2CID 12384262
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  17. ^ Craig C. Garner and Kang Shen. Structure and Function of Vertebrate and Invertebrate Active Zones. Structure and Functional Organization of the Synapse. Ed: Johannes Hell and Michael Ehlers. Springer, 2008.
  18. PMID 29739879
    .
  19. ^ a b Sherwood L., stikawy (2007). Human Physiology 6e: From Cells to Systems
  20. S2CID 34154835
    .
  21. ^
    ISBN 978-0-443-07145-4
    .
  22. ISBN 978-0-8153-3218-3
    .
  23. S2CID 20495134
    .
  24. S2CID 1323780
    .
  25. ^
    PMID 19865171
    .
  26. S2CID 30728927
    .
  27. ^ Kandel, Schwartz & Jessell 2000, p. 176
  28. ^ Hormuzdi et al. 2004
  29. PMID 15217338
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  30. PMID 12486148
    .
  31. PMID 4167209
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  32. S2CID 9527518
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  33. PMID 17068096
    .
  34. PMID 4320287
    .

References

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