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{{short description|Sort of synapse}} |
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[[File:SynapseSchematic en.svg|thumb |
[[File:SynapseSchematic en.svg|thumb|A diagram of a typical [[central nervous system]] synapse. The spheres located in the upper neuron contain [[neurotransmitter]]s that fuse with the [[presynaptic membrane]] and release neurotransmitters into the [[synaptic cleft]]. These neurotransmitters bind to receptors located on the [[postsynaptic membrane]] of the lower neuron, and, in the case of an excitatory synapse, may lead to a [[depolarization]] of the postsynaptic cell.]] |
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An '''excitatory synapse''' is a [[synapse]] in which an [[action potential]] in a [[presynaptic neuron]] increases the probability of an [[action potential]] occurring in a postsynaptic cell. |
An '''excitatory synapse''' is a [[synapse]] in which an [[action potential]] in a [[presynaptic neuron]] increases the probability of an [[action potential]] occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new [[action potential]] at its [[axon hillock]], thus transmitting the information to yet another cell.<ref name="Annual Review of Biochemistry">{{Cite journal|title=The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View |journal=Annual Review of Biochemistry |volume=76 |pages=823–47 |author1-link=Morgan Sheng |author1=M. Sheng |author2=C. Hoogenraad |year=2006|doi=10.1146/annurev.biochem.76.060805.160029 |pmid=17243894 |author2-link=Casper Hoogenraad }}</ref> |
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This phenomenon is known as an [[excitatory postsynaptic potential]] (EPSP). It may occur via direct contact between cells (i.e., via [[gap junction]]s), as in an [[electrical synapse]], but most commonly occurs via the [[vesicle (biology and chemistry)|vesicular]] release of [[neurotransmitter]]s from the [[presynaptic]] [[axon terminal]] into the [[synaptic cleft]], as in a [[chemical synapse]].<ref name="Journal of Cell Science">{{cite |
This phenomenon is known as an [[excitatory postsynaptic potential]] (EPSP). It may occur via direct contact between cells (i.e., via [[gap junction]]s), as in an [[electrical synapse]], but most commonly occurs via the [[vesicle (biology and chemistry)|vesicular]] release of [[neurotransmitter]]s from the [[presynaptic]] [[axon terminal]] into the [[synaptic cleft]], as in a [[chemical synapse]].<ref name="Journal of Cell Science">{{cite journal |title=Architecture of an Excitatory Synapse |journal=Journal of Cell Science |volume=123 |issue=6 |pages=819–823 |author1=Chua, Kindler |author2=Boykin, Jahn |date=2010-03-03|doi=10.1242/jcs.052696 |pmid=20200227 |hdl=11858/00-001M-0000-0012-D5F7-3 |s2cid=13491894 |hdl-access=free }}</ref> |
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The excitatory neurotransmitters, the most common of which is [[glutamate]], then migrate via [[diffusion]] to the [[dendritic spine]] of the postsynaptic neuron and bind a specific [[transmembrane receptor]] protein that triggers the [[depolarization]] of that cell.<ref name="Annual Review of Biochemistry"/> Depolarization, a deviation from a |
The excitatory neurotransmitters, the most common of which is [[glutamate]], then migrate via [[diffusion]] to the [[dendritic spine]] of the postsynaptic neuron and bind a specific [[transmembrane receptor]] protein that triggers the [[depolarization]] of that cell.<ref name="Annual Review of Biochemistry"/> Depolarization, a deviation from a neuron's [[Resting potential|resting membrane potential]] towards its [[threshold potential]], increases the likelihood of an action potential and normally occurs with the influx of positively charged [[sodium]] (Na<sup>+</sup>) ions into the postsynaptic cell through [[ion channel]]s activated by neurotransmitter binding. |
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==Chemical vs electrical synapses== |
==Chemical vs electrical synapses== |
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[[File:Synapse.theora.ogv|thumb |
[[File:Synapse.theora.ogv|thumb|Animation showing the function of a chemical synapse.]] |
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:There are two different kinds of synapses present within the human brain: chemical and electrical. Chemical synapses are by far the most prevalent and are the main player involved in excitatory synapses. Electrical synapses, the minority, allow direct, passive flow of electric current through special intercellular connections called gap junctions.<ref name="Neuroscience, 4th ed.">{{cite book |title=Neuroscience, 4th ed |author=D. Purves |publisher=Sinauer Associates, Inc. |location=Sunderland, Massachusetts |year=2008 | |
:There are two different kinds of synapses present within the human brain: chemical and electrical. Chemical synapses are by far the most prevalent and are the main player involved in excitatory synapses. Electrical synapses, the minority, allow direct, passive flow of electric current through special intercellular connections called gap junctions.<ref name="Neuroscience, 4th ed.">{{cite book |title=Neuroscience, 4th ed |author=D. Purves |publisher=Sinauer Associates, Inc. |location=Sunderland, Massachusetts |year=2008 |display-authors=etal }}</ref> These gap junctions allow for virtually instantaneous transmission of electrical signals through direct passive flow of ions between neurons (transmission can be bidirectional). The main goal of electrical synapses is to synchronize electrical activity among populations of neurons.<ref name="Neuroscience, 4th ed."/> The first electrical synapse was discovered in a [[caridoid escape reaction|crayfish]] nervous system.<ref name="Neuroscience, 4th ed."/> |
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:Chemical synaptic transmission is the transfer of neurotransmitters or [[neuropeptides]] from a presynaptic axon to a postsynaptic dendrite.<ref name="Neuroscience, 4th ed."/> Unlike an electrical synapse, the chemical synapses are separated by a space called the [[synaptic cleft]], typically measured between 15 and 25 nm. Transmission of an excitatory signal involves several steps outlined below. |
:Chemical synaptic transmission is the transfer of neurotransmitters or [[neuropeptides]] from a presynaptic axon to a postsynaptic dendrite.<ref name="Neuroscience, 4th ed."/> Unlike an electrical synapse, the chemical synapses are separated by a space called the [[synaptic cleft]], typically measured between 15 and 25 nm. Transmission of an excitatory signal involves several steps outlined below. |
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==Responses of the postsynaptic neuron== |
==Responses of the postsynaptic neuron== |
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:When neurotransmitters reach the postsynaptic neuron of an excitatory synapse, these molecules can bind to two possible types of receptors that are clustered in a protein-rich portion of the postsynaptic [[cytoskeleton]] called the [[Postsynaptic density]] (PSD).<ref name="Journal of Cell Science"/> Ionotropic receptors, which are also referred to as [[ligand-gated ion channel]]s, contain a transmembrane domain that acts as an ion channel and can directly open after binding of a neurotransmitter. [[Metabotropic receptor]]s, which are also called [[G-protein-coupled receptor]]s, act on an ion channel through the intracellular signaling of a molecule called a [[G protein]]. Each of these channels has a specific [[reversal potential]], E<sub>rev</sub>, and each receptor is selectively permeable to particular ions that flow either into or out of the cell in order to bring the overall membrane potential to this reversal potential.<ref name="Neuroscience, 4th ed."/> If a neurotransmitter binds to a receptor with a reversal potential that is higher than the threshold potential for the postsynaptic neuron, the postsynaptic cell will be more likely to generate an action potential and an excitatory postsynaptic potential will occur (EPSP). On the other hand, if the reversal potential of the receptor to which the neurotransmitter binds is lower than the threshold potential, an [[inhibitory postsynaptic potential]] will occur (IPSP).<ref name="National Center for Biotechnology Information">{{cite |
:When neurotransmitters reach the postsynaptic neuron of an excitatory synapse, these molecules can bind to two possible types of receptors that are clustered in a protein-rich portion of the postsynaptic [[cytoskeleton]] called the [[Postsynaptic density]] (PSD).<ref name="Journal of Cell Science"/> Ionotropic receptors, which are also referred to as [[ligand-gated ion channel]]s, contain a transmembrane domain that acts as an ion channel and can directly open after binding of a neurotransmitter. [[Metabotropic receptor]]s, which are also called [[G-protein-coupled receptor]]s, act on an ion channel through the intracellular signaling of a molecule called a [[G protein]]. Each of these channels has a specific [[reversal potential]], E<sub>rev</sub>, and each receptor is selectively permeable to particular ions that flow either into or out of the cell in order to bring the overall membrane potential to this reversal potential.<ref name="Neuroscience, 4th ed."/> If a neurotransmitter binds to a receptor with a reversal potential that is higher than the threshold potential for the postsynaptic neuron, the postsynaptic cell will be more likely to generate an action potential and an excitatory postsynaptic potential will occur (EPSP). On the other hand, if the reversal potential of the receptor to which the neurotransmitter binds is lower than the threshold potential, an [[inhibitory postsynaptic potential]] will occur (IPSP).<ref name="National Center for Biotechnology Information">{{cite journal |url=https://www.ncbi.nlm.nih.gov/books/NBK11117 |title=Excitatory and Inhibitory Postsynaptic Potentials |publisher=Sinauer Associates, Inc. |year=2001|last1=Williams |first1=S. Mark |last2=McNamara |first2=James O. |last3=Lamantia |first3=Anthony-Samuel |last4=Katz |first4=Lawrence C. |last5=Fitzpatrick |first5=David |last6=Augustine |first6=George J. |last7=Purves |first7=Dale }}</ref> |
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:Although the receptors at an excitatory synapse strive to bring the membrane potential towards their own specific E<sub>rev</sub>, the probability that the single stimulation of an excitatory synapse will raise the membrane potential past threshold and produce an action potential is not very high. Therefore, in order to achieve threshold and generate an action potential, the postsynaptic neuron has the capacity to add up all of the incoming EPSPs based on the mechanism of [[Summation (neurophysiology)|summation]], which can occur in time and space. Temporal summation occurs when a particular synapse is stimulated at a high frequency, which causes the postsynaptic neuron to sum the incoming EPSPs and thus increases the chance of the neuron firing an action potential. In a similar way, the postsynaptic neuron can sum together EPSPs from multiple synapses with other neurons in a process called spatial summation.<ref name="Neuroscience, 4th ed."/> |
:Although the receptors at an excitatory synapse strive to bring the membrane potential towards their own specific E<sub>rev</sub>, the probability that the single stimulation of an excitatory synapse will raise the membrane potential past threshold and produce an action potential is not very high. Therefore, in order to achieve threshold and generate an action potential, the postsynaptic neuron has the capacity to add up all of the incoming EPSPs based on the mechanism of [[Summation (neurophysiology)|summation]], which can occur in time and space. Temporal summation occurs when a particular synapse is stimulated at a high frequency, which causes the postsynaptic neuron to sum the incoming EPSPs and thus increases the chance of the neuron firing an action potential. In a similar way, the postsynaptic neuron can sum together EPSPs from multiple synapses with other neurons in a process called spatial summation.<ref name="Neuroscience, 4th ed."/> |
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===Excitotoxicity=== |
===Excitotoxicity=== |
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{{main|Excitotoxicity}} |
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:''Main Article'': [[Excitotoxicity]] |
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====Pathophysiology==== |
====Pathophysiology==== |
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:Since glutamate is the most common excitatory neurotransmitter involved in synaptic neuronal transmission, it follows that disruptions in the normal functioning of these pathways can have severe detrimental effects on the nervous system. A major source of cellular stress is related to glutaminergic overstimulation of a postsynaptic neuron via excessive activation of glutamate receptors (i.e., [[NMDA Receptor|NMDA]] and [[AMPA Receptor|AMPA]] receptors), a process known as excitotoxicity, which was first discovered accidentally by D. R. Lucas and J. P. Newhouse in 1957 during experimentation on sodium-fed lab mice.<ref name="Neuroscience, 4th ed."/> |
:Since glutamate is the most common excitatory neurotransmitter involved in synaptic neuronal transmission, it follows that disruptions in the normal functioning of these pathways can have severe detrimental effects on the nervous system. A major source of cellular stress is related to glutaminergic overstimulation of a postsynaptic neuron via excessive activation of glutamate receptors (i.e., [[NMDA Receptor|NMDA]] and [[AMPA Receptor|AMPA]] receptors), a process known as excitotoxicity, which was first discovered accidentally by D. R. Lucas and J. P. Newhouse in 1957 during experimentation on sodium-fed lab mice.<ref name="Neuroscience, 4th ed."/> |
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:Under normal conditions, extracellular glutamate levels are held under strict control by surrounding neuronal and [[glial cell]] [[Membrane transport protein|membrane transporters]], rising to a concentration of about 1 mM and quickly falling to resting levels.<ref name="Science Daily">{{cite web |url= |
:Under normal conditions, extracellular glutamate levels are held under strict control by surrounding neuronal and [[glial cell]] [[Membrane transport protein|membrane transporters]], rising to a concentration of about 1 mM and quickly falling to resting levels.<ref name="Science Daily">{{cite web |url=https://www.sciencedaily.com/articles/e/excitotoxicity.htm |title=Excitotoxicity and Cell Damage |year=2010}}</ref> These levels are maintained via the recycling of glutamate molecules in the neuronal-glial cell process known as the [[glutamate–glutamine cycle]], in which glutamate is [[Chemical synthesis|synthesized]] from its precursor [[glutamine]] in a controlled manner in order to maintain an adequate supply of the neurotransmitter.<ref name="Neuroscience, 4th ed."/> However, when glutamate molecules in the synaptic cleft cannot be degraded or reused, often due to dysfunction of the glutamate–glutamine cycle, the neuron becomes significantly overstimulated, leading to a neuronal cell death pathway known as [[apoptosis]]. Apoptosis occurs primarily via the increased intracellular concentrations of calcium ions, which flow into the cytosol through the activated glutamate receptors and lead to the activation of [[phospholipase]]s, [[endonuclease]]s, [[protease]]s, and thus the apoptotic cascade. Additional sources of neuronal cell death related to excitotoxicity involve energy rundown in the [[mitochondria]] and increased concentrations of reactive [[Reactive oxygen species|oxygen]] and [[reactive nitrogen species|nitrogen]] species within the cell.<ref name="Neuroscience, 4th ed."/> |
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====Treatment==== |
====Treatment==== |
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:Excitotoxic mechanisms are often involved in other conditions leading to neuronal damage, including [[hypoglycemia]], [[trauma (medicine)|trauma]], [[stroke]], [[seizure]]s, and many neurodegenerative diseases, and thus have important implications in disease treatment. Recent studies have been performed that incorporate glutamate [[receptor antagonist]]s and excitotoxic cascade disruptors in order to decrease stimulation of postsynaptic neurons, although these treatments are still undergoing active research.<ref name="Biochemical Pharmacology">{{cite |
:Excitotoxic mechanisms are often involved in other conditions leading to neuronal damage, including [[hypoglycemia]], [[trauma (medicine)|trauma]], [[stroke]], [[seizure]]s, and many neurodegenerative diseases, and thus have important implications in disease treatment. Recent studies have been performed that incorporate glutamate [[receptor antagonist]]s and excitotoxic cascade disruptors in order to decrease stimulation of postsynaptic neurons, although these treatments are still undergoing active research.<ref name="Biochemical Pharmacology">{{cite journal |title=Novel treatment of excitotoxicity: targeted disruption of intracellular signalling from glutamate receptors |author1=M. Aarts |author2=M. Tymianski |date=2003-09-15 |doi=10.1016/S0006-2952(03)00297-1 |volume=66 |issue=6 |journal=Biochemical Pharmacology |pages=877–886 |pmid=12963474}}</ref> |
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===Related neurodegenerative diseases=== |
===Related neurodegenerative diseases=== |
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:[[Alzheimer's |
:[[Alzheimer's disease]] (AD) is the most common form of neurodegenerative [[dementia]], or loss of brain function, and was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1907. 9. <ref name="Disease Management Project">{{cite web |url=http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/alzheimers-disease/ |title=Alzheimer's Disease |author1=J. Tavee |author2=P. Sweeney }}</ref> Diagnosis of the disease often stems from clinical observation as well as analysis of family history and other risk factors, and often includes symptoms such as memory impairment and problems with language, decision-making, judgment, and personality.<ref name="Pub-Med Health: Diseases and Conditions">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001767/ |title=Alzheimer's Disease |date=2010-10-04}}</ref> The primary neurological phenomena that lead to the above symptoms are often related to signaling at excitatory synapses, often due to excitotoxicity, and stem from the presence of [[amyloid plaque]]s and [[neurofibrillary tangle]]s, as well as neuronal cell death and synaptic pruning. The principle drug treatments on the market deal with antagonizing glutamate (NMDA) receptors at neuronal synapses, and inhibiting the activity of [[acetylcholinesterase]]. This treatment aims to limit the apoptosis of cerebral neurons caused by various pathways related to excitotoxicity, free radicals, and energy rundown. A number of labs are currently focusing on the prevention of amyloid plaques and other AD symptoms, often via the use of experimental [[vaccine]]s, although this area of research is yet in its infancy.<ref name="Disease Management Project"/> |
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[[File:Histological sample of Substantia nigra in Parkinson's disease.jpg|thumb|Histological brain sample of the Substantia Nigra in Parkinson's disease, showing the presence of Lewy bodies and other signs of neurodegeneration.]] |
[[File:Histological sample of Substantia nigra in Parkinson's disease.jpg|thumb|Histological brain sample of the Substantia Nigra in Parkinson's disease, showing the presence of Lewy bodies and other signs of neurodegeneration.]] |
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:[[Parkinson's |
:[[Parkinson's disease]] (PD) is a neurodegenerative disease resulting from the apoptosis of [[dopamine|dopaminergic neurons]] in the central nervous system, especially the [[substantia nigra]], as well as heightened response to the excitatory neurotransmitter, glutamate (i.e., excitotoxicity).<ref name="Parkinsonism and Related Disorders">{{cite journal |title=Excitotoxicity and New Antiglutamatergic Strategies in Parkinson's disease and Alzheimer's disease |author1=E. Koutsilieri |author2=P. Riederera |year=2007 |doi=10.1016/S1353-8020(08)70025-7 |pmid=18267259 |volume=13 |journal=Parkinsonism & Related Disorders |pages=S329–S331}}</ref> While the most obvious symptoms are related to motor skills, prolonged progression of the disease can lead to cognitive and behavioral problems as well as dementia. Although the mechanism of apoptosis in the brain is not entirely clear, speculation associates cell death with abnormal accumulation of [[ubiquitin]]ated proteins in cell occlusions known as [[Lewy body|Lewy bodies]], as well as hyperstimulation of neuronal NMDA receptors with excessive glutamate neurotransmitter via the aforementioned pathway.<ref name="Parkinsonism and Related Disorders"/> Like Alzheimer's, Parkinson's Disease lacks a cure. Therefore, in addition to lifestyle changes and surgery, the goal of pharmaceutical drugs used in the treatment of PD patients is to control symptoms and limit, when possible, the progression of the disease. [[Levodopa|Levodopa (L-DOPA)]], the most widely used treatment of PD, is converted to dopamine in the body and helps to relieve the effect of decreased dopaminergic neurons in the central nervous system. Other dopamine [[agonist]]s have been administered to patients in an effort to mimic dopamine’s effect at excitatory synapses, binding its receptors and causing the desired postsynaptic response.<ref name="Pub-Med Health: Diseases and Conditions – PD">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001762/ |title=Parkinson's Disease |year=2011}}</ref> |
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==See also== |
==See also== |
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{{DEFAULTSORT:Excitatory Synapse}} |
{{DEFAULTSORT:Excitatory Synapse}} |
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[[Category: |
[[Category:Neural synapse]] |
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[[Category:Articles containing video clips]] |
[[Category:Articles containing video clips]] |
Anexcitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell.[1]
This phenomenon is known as an excitatory postsynaptic potential (EPSP). It may occur via direct contact between cells (i.e., via gap junctions), as in an electrical synapse, but most commonly occurs via the vesicular release of neurotransmitters from the presynaptic axon terminal into the synaptic cleft, as in a chemical synapse.[2]
The excitatory neurotransmitters, the most common of which is glutamate, then migrate via diffusion to the dendritic spine of the postsynaptic neuron and bind a specific transmembrane receptor protein that triggers the depolarization of that cell.[1] Depolarization, a deviation from a neuron's resting membrane potential towards its threshold potential, increases the likelihood of an action potential and normally occurs with the influx of positively charged sodium (Na+) ions into the postsynaptic cell through ion channels activated by neurotransmitter binding.
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