Illustration of the major elements in a prototypical synapse. Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical impulses into chemical signals. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell Dendrites (from Greek δένδρον déndron, “tree” are the branched projections of a Neuron that act to conduct the electrochemical In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal See Chemical synapse for an introduction to concepts and terminology used in this article

Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the A gland is an organ in an animal's body that synthesizes a substance for release such as Hormones or Breast milk, often into the Bloodstream Chemical synapses allow neurons to form interconnected circuits within the central nervous system. In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. They are thus crucial to the biological computations that underlie perception and thought. They provide the means through which the nervous system connects to and controls the other systems of the body, for example the specialized synapse between a motor neuron and a muscle cell is called a neuromuscular junction. A neuromuscular junction ( NMJ) is the Synapse or junction of the Axon terminal of a Motoneuron with the motor end plate, the

Young children have about 10¹⁶ synapses (10 quadrillion). This number declines with age, stabilizing by adulthood. Estimates for adults vary from 10¹⁵ to 5 × 10¹⁵ (1-5 quadrillion) synapses.

The word "synapse" comes from "synaptein", which Sir Charles Scott Sherrington and colleagues coined from the Greek "syn-" ("together") and "haptein" ("to clasp"). Sir Charles Scott Sherrington OM, GBE, PRS ( November 27, 1857 - March 4, 1952) was an English neurophysiologist Chemical synapses are not the only type of biological synapse: electrical and immunological synapses exist as well. An electrical synapse is a mechanical and electrically conductive link between two abutting Neuron cells that is formed at a narrow gap between the pre- In Immunology, an immunological synapse is the interface between an Antigen-presenting cell and a Lymphocyte. Without a qualifier, however, "synapse" commonly refers to a chemical synapse.

Structure

a diagram of a nerve cell showing the different places where a synapse could occur

Chemical synapses pass information directionally from a presynaptic cell to a postsynaptic cell and are therefore asymmetric in structure and function. The presynaptic terminal, or synaptic bouton, is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane bound spheres called synaptic vesicles. An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell See Chemical synapse for an introduction to concepts and terminology used in this article In a Neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various Neurotransmitters that are released during Calcium -regulated Synaptic vesicles are docked at the presynaptic plasma membrane at regions called active zones (AZ). The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer

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. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling Dendrites (from Greek δένδρον déndron, “tree” are the branched projections of a Neuron that act to conduct the electrochemical Immediately behind the postsynaptic membrane is an elaborate complex of interlinked proteins called the postsynaptic density (PSD). The postsynaptic density ( PSD) is a cytoskeleton specialization at neuronal Synapses that was originally identified as an electron-dense region at the membrane of a

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. A dendritic spine (or spine is a small membranous protrusion from a neuron's Dendrite that typically receives input from a single Synapse

Between the pre- and postsynaptic cells is a gap about 20nm wide called the synaptic cleft. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands The small volume of the cleft allows neurotransmitter concentration to be raised and lowered rapidly. The membranes of the two adjacent cells are held together by cell adhesion proteins. Cellular adhesion is the binding of a cell to another cell or to a Surface or matrix. ^[1]

Signaling across chemical synapses

Neurotransmitter release

The release of a neurotransmitter is triggered by the arrival of a nerve impulse (or action potential) and occurs through an unusually rapid process of cellular secretion, also known as exocytosis: Within the presynaptic nerve terminal, vesicles containing neurotransmitter sit "docked" and ready at the synaptic membrane. In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal Exocytosis (ek-soh-sy-TOH-sis Greek: Έξω - external and κύτος - cell is the durable process by which a cell directs secretory vesicles out of the Cell A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels at the down stroke of the action potential (tail current). In Cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signaling whereby a diffusable signaling molecule Voltage-dependent calcium channels (VDCC are a group of voltage-gated Ion channels found in excitable cells ( e ^[2] Calcium ions then trigger a biochemical cascade which results in vesicles fusing with the presynaptic membrane and releasing their contents to the synaptic cleft within 180µsec of calcium entry. To help compare Orders of magnitude of different Times this page lists times between 10&minus6 seconds and 10&minus5 seconds (1 micro ^[2] Vesicle fusion is driven by the action of a set of proteins in the presynaptic terminal known as SNAREs. SNARE proteins (an Acronym derived from "soluble NSF attachment receptor" are a large protein superfamily consisting of more than 60 members in yeast

The membrane added by this fusion is later retrieved by endocytosis and recycled for the formation of fresh neurotransmitter-filled vesicles. Endocytosis is a process where cells absorb material ( Molecules such as proteins from the outside by engulfing it with their Cell membrane. Most animal cells take up portions of their surface Plasma membranes in a process called Endocytosis.

Receptor binding

Receptors on the opposite side of the synaptic gap bind neurotransmitter molecules and respond by opening nearby ion channels in the postsynaptic cell membrane, causing ions to rush in or out and changing the local transmembrane potential of the cell. Membrane potential (or transmembrane potential) is the Voltage difference (or Electrical potential difference between the interior and exterior of a The resulting change in voltage is called a postsynaptic potential. Electrical tension (or voltage after its SI unit, the Volt) is the difference of electrical potential between two points of an electrical Postsynaptic potentials are changes in the Membrane potential of the postsynaptic terminal of a Chemical synapse. In general, the result is excitatory, in the case of depolarizing currents, or inhibitory in the case of hyperpolarizing currents. In biology depolarization is a decrease in the Absolute value of a cell's Membrane potential. Whether a synapse is excitatory or inhibitory depends on what type(s) of ion channel conduct the postsynaptic current display(s), which in turn is a function of the type of receptors and neurotransmitter employed at the synapse.

Termination

The signal is terminated by either breakdown of neurotransmitters, or reuptake, the latter is mainly in the presynaptic neuron to avail recycling of the transmitter.

Reuptake

Following fusion of the synaptic vesicles and release of transmitter molecules into the synaptic cleft, small neurotransmitters, such as glycine, are rapidly cleared from the space for recycling by specialized membrane proteins in the presynaptic or postsynaptic membrane. Glycine (abbreviated as Gly or G) is the Organic compound with the formula NH2CH2COOH

Breakdown

Some neurotransmitters, e. g. acetylcholine and large ones such as peptides, are broken down without any direct reuptake. The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino The choline part of acetylcholine, however, is to a large degree taken up by the presynaptic neuron for recycling. Choline is an Organic compound, classified as a water-soluble Essential nutrient and usually grouped within the Vitamin B complex Peptides, on the other hand, must be resynthesized from the neuron soma. The soma, or cyton or perikaryon, is the bulbous end of a Neuron, containing the Cell nucleus.

Modulation of synaptic transmission

Synaptic transmission can be modulated by e. g. desensitization, homotropic and heterotropic modulation:

Desensitization

Main article: 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. Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule

Homotropic modulation

Homotropic modulation is a modulation of the presynaptic neuron by its own neurotransmitters, i. e. a form of autocrine signaling. Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent that binds to autocrine receptors on the same cell leading The modulation can include size, number and replenishment rate of vesicles. It is often inhibitory, with the effect of presynaptic inhibition, making the neurotransmitter self-regulating.

One example are neurons of the sympathetic nervous system (SNS), which release noradrenaline, which, besides from affecting postsynaptic receptors, also affect α2-adrenergic receptors, inhibiting further release of noradrenaline. The Sympathetic Nervous System ( SNS) is a branch of the Autonomic nervous system along with the Enteric nervous system and Parasympathetic nervous Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors ^[3] This effect is utilized with clonidine to perform inhibitory effects on the SNS. Clonidine is a direct-acting α2 Adrenergic agonist prescribed historically as an Antihypertensive agent

Heterotropic modulation

Heterotropic modulation is a modulation of presynaptic terminals of nearby neurons. Again, the modulation can include size, number and replenishment rate of vesicles.

One example are again neurons of the sympathetic nervous system, which release noradrenaline, which, in addition, generate inhibitory effect on presynaptic terminals of neurons of the parasympathetic nervous system. The Sympathetic Nervous System ( SNS) is a branch of the Autonomic nervous system along with the Enteric nervous system and Parasympathetic nervous Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a The parasympathetic Nervous system ( PSNS) is a division of the Autonomic nervous system (ANS along with the Sympathetic nervous system ^[3]

Pharmacological intervention

For example, a class of drugs known as selective serotonin reuptake inhibitors or SSRIs affect certain synapses by inhibiting the reuptake of the neurotransmitter serotonin. Reuptake, or re-uptake, is the reabsorption of a Neurotransmitter by the Neurotransmitter transporter of a pre-synaptic Neuron after Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons In contrast, one important excitatory neurotransmitter, acetylcholine, is first broken down into acetate and choline by the enzyme acetylcholinesterase prior to removal from the synapse. The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central An acetate, or ethanoate, is either a salt or Ester of Acetic acid. Choline is an Organic compound, classified as a water-soluble Essential nutrient and usually grouped within the Vitamin B complex

Integration of synaptic inputs

In general, if an excitatory synapse is strong, an action potential in the presynaptic neuron will trigger another in the postsynaptic cell, whereas, at a weak synapse, the excitatory postsynaptic potential ("EPSP") will not reach the threshold for action potential initiation. In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal In Neuroscience, an excitatory postsynaptic potential ( EPSP) is a temporary depolarization of postsynaptic Membrane potential caused by the flow of positively In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal In the brain, however, each neuron forms synapses with many others, and, likewise, each receives synaptic inputs from many others. When action potentials fire simultaneously in several neurons that weakly synapse on a single cell, they may initiate an impulse in that cell even though the synapses are weak. This process is known as summation. ^[4] On the other hand, a presynaptic neuron releasing an inhibitory neurotransmitter such as GABA can cause inhibitory postsynaptic potential in the postsynaptic neuron, decreasing its excitability and therefore decreasing the neuron's likelihood of firing an action potential. Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. An Inhibitory Postsynaptic Potential (commonly abbreviated as IPSP) is the change in membrane voltage of a postsynaptic Neuron which results from synaptic In this way, the output of a neuron may depend on the input of many others, each of which may have a different degree of influence, depending on the strength of its synapse with that neuron. John Carew Eccles performed some of the important early experiments on synaptic integration, for which he received the Nobel Prize for Physiology or Medicine in 1963. Sir John Carew Eccles, AC FRS FRACP FRSNZ FAAS ( January 27, 1903 &ndash May 2, 1997 The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. Complex input/output relationships form the basis of transistor-based computations in computers, and are thought to figure similarly in neural circuits. In Electronics, a transistor is a Semiconductor device commonly used to amplify or switch electronic signals A computer is a Machine that manipulates data according to a list of instructions.

Synaptic strength

The strength of a synapse is defined by the change in transmembrane potential resulting from activation of the postsynaptic neurotransmitter receptors. This change in voltage is known as a postsynaptic potential, and is a direct result of ionic currents flowing through the postsynaptic ion channels. Electric current is the flow (movement of Electric charge. The SI unit of electric current is the Ampere. Changes in synaptic strength can be short–term and without permanent structural changes in the neurons themselves, lasting seconds to minutes — or long-term (long-term potentiation, or LTP), in which repeated or continuous synaptic activation can result in second messenger molecules initiating protein synthesis, resulting in alteration of the structure of the synapse itself. In Neuroscience, long-term potentiation ( LTP) is the long-lasting improvement in communication between two Neurons that results from stimulating them In Cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signaling whereby a diffusable signaling molecule Protein synthesis is the creation of proteins using DNA and' RNA'. Learning and memory are believed to result from long-term changes in synaptic strength, via a mechanism known as synaptic plasticity. In Neuroscience, synaptic plasticity is the ability of the connection or Synapse, between two Neurons to change in strength.

Relationship to electrical synapses

An electrical synapse is a mechanical and electrically conductive link between two abutting neurons that is formed at a narrow gap between the pre- and postsynaptic cells known as a gap junction. An electrical synapse is a mechanical and electrically conductive link between two abutting Neuron cells that is formed at a narrow gap between the pre- In Science and engineering, a conductor is a material which contains movable Electric charges. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called A gap junction or nexus is a specialized Intercellular connection between certain animal cell -types At gap junctions, cells approach within about 3. 5 nm of each other, rather than the 20 to 40 nm distance that separates cells at chemical synapses. A nanometre ( American spelling: nanometer, symbol nm) ( Greek: νάνος nanos dwarf; μετρώ metrό count) is a ^[5][6] As opposed to chemical synapses, the postsynaptic potential in electrical synapses is not caused by the opening of ion channels by chemical transmitters, but by direct electrical coupling between both neurons. Electrical synapses are therefore faster^[1] and more reliable than chemical synapses. Electrical synapses are found throughout the nervous system, yet are less common than chemical synapses.

See also

• Postsynaptic potential

• Excitatory postsynaptic potential
• Inhibitory postsynaptic potential

• Immunological synapse
• Neuromuscular junction
• Neurotransmitter
• Receptor
• Exocytosis

Notes

References

• Kandel, Eric R.; James H. Eric Richard Kandel (born November 7, 1929) is a Psychiatrist, a neuroscientist and Professor of Biochemistry Schwartz, Thomas M. Jessell (2000). Principles of Neural Science, 4th edition, New York: McGraw-Hill. First published in 1981 by Elsevier, Principles of Neural Science is a Neuroscience Textbook edited by Eric R ISBN 0-8385-7701-6.  
• Llinas R. Sugimori M. and Simon S. M. (1982) PNAS 79:2415-2419
• Llinás R, Steinberg IZ, and Walton K (1981). "{{{title}}}". Biophysical Journal 33.  
• Bear, Mark; Mark F. Bear, Barry W. Connors, Michael A. Paradiso (2001). Neuroscience: Exploring the Brain. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-3944-6.  
• Hormuzdi, SG; Filippov MA, Mitropoulou G, Monyer H, Bruzzone R. (Mar 2004). "Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks". Biochim Biophys Acta 1662 (1-2): 113-137. doi:10.1016/j.bbamem.2003.10.023. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. ISSN 0005-2736. An International Standard Serial Number ( ISSN) is a unique eight-digit number used to identify a print or electronic Periodical publication. PMID 15033583.  
• Karp, Gerald (2005). Cell and Molecular Biology: concepts and experiments, 4th edition, Hoboken, NJ: John Wiley & Sons, Inc. . ISBN 0-471-46580-1.  .
• Nicholls, J. G. ; Martin A. R. , Wallace B. G. , Fuchs P. A. (2001). From Neuron to Brain, 4th edition, Sunderland, MA: Sinauer Associates. ISBN 0878934391.  

External links

• Synapse Review for Kids
• Biologymad. com (2004) Synapses