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'''Schaffer collaterals''' are [[axon]] collaterals given off by CA3 [[pyramidal cell]]s in the [[hippocampus]]. These collaterals project to area CA1 of the hippocampus<ref name="Vago">Vago DR, Kesner RP(2008). Disruption of the direct [[perforant path]] input to the CA1 subregion of the [[Dorsum (anatomy)|dorsal]] hippocampus interferes with spatial [[working memory]] and novelty detection. Behav. Brain Res. 189(2): 273–83</ref> and are an integral part of [[memory]] formation and the [[emotion]]al network of the [[Papez circuit]], and of the [[hippocampus|hippocampal]] [[trisynaptic loop]]. It is one of the most studied [[synapse]]s in the world and named after the Hungarian [[anatomist]]-[[neurologist]] [[Károly Schaffer]].
'''Schaffer collaterals''' are [[axon]] collaterals given off by CA3 [[pyramidal cell]]s in the [[hippocampus]]. These collaterals project to area CA1 of the hippocampus<ref name="Vago">{{cite journal |last1=Vago |first1=David R. |last2=Kesner |first2=Raymond P. |title=Disruption of the direct perforant path input to the CA1 subregion of the dorsal hippocampus interferes with spatial working memory and novelty detection |journal=Behavioural Brain Research |date=June 2008 |volume=189 |issue=2 |pages=273–283 |doi=10.1016/j.bbr.2008.01.002 |pmid=18313770 |pmc=2421012}}</ref> and are an integral part of memory formation and the [[emotion]]al network of the [[Papez circuit]], and of the [[hippocampus|hippocampal]] [[trisynaptic loop]]. It is one of the most studied [[synapse]]s in the world and named after the Hungarian [[anatomist]]-[[neurologist]] [[Károly Schaffer]].


As a part of the hippocampal structures, Schaffer collaterals develop the [[limbic system]], which plays a critical role in the aspects of learning and memory. The signals of information from the contralateral CA3 region leave via the Schaffer collateral pathways for the CA1 [[pyramidal neuron]]s. Mature synapses contain fewer Schaffer collateral branches than those synapses that are not fully developed.<ref name="Schiess">Schiess AR, Scullin C & Partridge LD (2010). Maturation of Schaffer collateral synapses generates a [[phenotype]] of unreliable basal evoked release and very reliable facilitated release. ''European Journal of Neuroscience''. 31:1377-1387.</ref> Many scientists try to use the Schaffer collateral synapse as a sample synapse, a typical excitatory [[glutamatergic]] synapse in the [[Cerebral cortex|cortex]] that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well and to develop medication and treatment to cure the [[chronic diseases]], such as [[dementia]] and [[Alzheimer's disease]]. Moreover, they believe that studying the Schaffer collateral can provide a whole range of understanding how Schaffer collaterals allow us to intervene with drug-treatments and with electrical-stimulation so that the quality of human experience can be improved.
As a part of the hippocampal structures, Schaffer collaterals develop the [[limbic system]], which plays a critical role in the aspects of learning and memory. The signals of information from the contralateral CA3 region leave via the Schaffer collateral pathways for the CA1 [[pyramidal neuron]]s. Mature synapses contain fewer Schaffer collateral branches than those synapses that are not fully developed.<ref name="Schiess"/> Many scientists try to use the Schaffer collateral synapse as a sample synapse, a typical excitatory [[glutamatergic]] synapse in the [[Cerebral cortex|cortex]] that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well and to develop medication and treatment to cure the [[chronic diseases]], such as [[dementia]] and [[Alzheimer's disease]]. Moreover, they believe that studying the Schaffer collateral can provide a whole range of understanding how Schaffer collaterals allow us to intervene with drug-treatments and with electrical-stimulation so that the quality of human experience can be improved.


==Development==
==Development==
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The Schaffer collateral is involved in [[activity-dependent plasticity]] and the information processes that always are processed through the hippocampus all the time. The Schaffer collateral clearly affects whether the target cells fire [[action potential]]s or not. However, at the same time, it is triggering the process that takes much longer whereby some [[synapse]]s get stronger and some get weaker, and overall the patterns of [[synaptic strength]] of the network all evolve over time.
The Schaffer collateral is involved in [[activity-dependent plasticity]] and the information processes that always are processed through the hippocampus all the time. The Schaffer collateral clearly affects whether the target cells fire [[action potential]]s or not. However, at the same time, it is triggering the process that takes much longer whereby some [[synapse]]s get stronger and some get weaker, and overall the patterns of [[synaptic strength]] of the network all evolve over time.


Moreover, Schaffer collateral [[axon]]s develop [[excitatory synapse]]s that are scattered over the [[Dendrite|dendritic]] arborization<ref>[http://www.thefreedictionary.com/arborization]</ref> of [[hippocampal]] [[Cornu Ammonis area 1|CA1]] pyramidal [[neuron]]s.<ref name="Smith">Smith MA, Ellis-Davies GC & Magee JC (2003).
Moreover, Schaffer collateral [[axon]]s develop [[excitatory synapse]]s that are scattered over the [[Dendrite|dendritic]] arborization<ref>{{cite web |title=arborization |url=http://www.thefreedictionary.com/arborization |website=The Free Dictionary}}</ref> of [[hippocampal]] [[Cornu Ammonis area 1|CA1]] pyramidal [[neuron]]s.<ref name="Smith">{{cite journal |last1=Smith |first1=M. A |last2=Ellis-Davies |first2=G. C R |last3=Magee |first3=J. C |title=Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons |journal=The Journal of Physiology |date=21 February 2003 |volume=548 |issue=1 |pages=245–258 |doi=10.1113/jphysiol.2002.036376 |pmid=12598591 |pmc=2342790}}</ref> In the early stage of [[long-term potentiation]], Schaffer collaterals release [[glutamate]] that binds to [[AMPA receptor]]s of CA1-[[dendrite]]s. The process of developing a network of CA3-to-CA1 recurrent [[excitatory]] [[glutamatergic]] synapses alters the [[frequency]] of spontaneous [[action potential]]s in Schaffer collaterals. By adulthood, CA3 recurrent network activity is reduced, the frequency of spontaneous action potentials is decreased in Schaffer collaterals, and a single release locus synapse with one [[dendritic spine]] on a given CA1 pyramidal neuron can be developed by Schaffer collateral axons.<ref name="Schiess" />
Mechanism of the distance-dependent scaling of Schaffer collateral [[synapse]]s in rat [[Cornu Ammonis area 1|CA1]] pyramidal neurons. ''Journal of Physiology''. 548.1:245-258</ref> In the early stage of [[long-term potentiation]], Schaffer collaterals release [[glutamate]] that binds to [[AMPA receptor]]s of CA1-[[dendrite]]s. The process of developing a network of CA3-to-CA1 recurrent [[excitatory]] [[glutamatergic]] synapses alters the [[frequency]] of spontaneous [[action potential]]s in Schaffer collaterals. By adulthood, CA3 recurrent network activity is reduced, the frequency of spontaneous action potentials is decreased in Schaffer collaterals, and a single release locus synapse with one [[dendritic spine]] on a given CA1 pyramidal neuron can be developed by Schaffer collateral axons.<ref name="Schiess" />


==Location==
==Location==
<!-- Deleted image removed: [[File:Researcb Design.png|left|alt=A hippocampal cartoon shows CA3-Schaffer collateral-CA1.]] -->
<!-- Deleted image removed: [[File:Researcb Design.png|left|alt=A hippocampal cartoon shows CA3-Schaffer collateral-CA1.]] -->
The Schaffer collateral is located between the [[Cornu Ammonis area 3|CA3]] region and [[Cornu Ammonis area 1|CA1]] region in the [[hippocampus]]. Schaffer collaterals are the axons of [[pyramidal cell]]s that connect two [[neuron]]s (CA3 and CA1) and transfer information from CA3 to CA1.<ref name="Lebeau">Lebeau G, DesGroseillers L, Sossin Wayne & Lacaille J (2011). [[mRNA]] binding [[protein]] [[staufen (protein)|staufen]] 1-dependent regulation of pyramidal cell spine morphology [[NMDA receptor]] mediated [[synaptic plasticity]]. ''BioMed central''. 4(22)</ref><ref name="Arrigoni">Arrigoni E & Greene RW (2004). Schaffer collateral and [[perforant path]] inputs activate different subtypes of [[NMDA receptor]]s on the same CA1 pyramidal cell. ''[[British Journal of Pharmacology]]''. 142: 317-322</ref> The [[entorhinal cortex]] sends the main input to the [[dentate gyrus]] ([[perforant path]]way). From the [[granule cell]]s of the dentate gyrus, connections are made to the CA3 regions of the hippocampus via [[mossy fiber (hippocampus)|mossy fibers]]. CA3 sends the information signals to CA1 pyramidal cells via the Schaffer collateral and [[commissural fiber]]s from the [[contralateral]] hippocampus as well.
The Schaffer collateral is located between the [[Cornu Ammonis area 3|CA3]] region and [[Cornu Ammonis area 1|CA1]] region in the [[hippocampus]]. Schaffer collaterals are the axons of [[pyramidal cell]]s that connect two [[neuron]]s (CA3 and CA1) and transfer information from CA3 to CA1.<ref name="Lebeau">{{cite journal |last1=Lebeau |first1=Geneviève |last2=DesGroseillers |first2=Luc |last3=Sossin |first3=Wayne |last4=Lacaille |first4=Jean-Claude |title=mRNA binding protein staufen 1-dependent regulation of pyramidal cell spine morphology via NMDA receptor-mediated synaptic plasticity |journal=Molecular Brain |date=2011 |volume=4 |issue=1 |pages=22 |doi=10.1186/1756-6606-4-22 |pmid=21635779 |pmc=3118231}}</ref><ref name="Arrigoni">{{cite journal |last1=Arrigoni |first1=Elda |last2=Greene |first2=Robert W |title=Schaffer collateral and perforant path inputs activate different subtypes of NMDA receptors on the same CA1 pyramidal cell |journal=[[British Journal of Pharmacology]] |date=May 2004 |volume=142 |issue=2 |pages=317–322 |doi=10.1038/sj.bjp.0705744 |pmid=15155538 |pmc=1574942}}</ref> The [[entorhinal cortex]] sends the main input to the [[dentate gyrus]] ([[perforant path]]way). From the [[granule cell]]s of the dentate gyrus, connections are made to the CA3 regions of the hippocampus via [[mossy fiber (hippocampus)|mossy fibers]]. CA3 sends the information signals to CA1 pyramidal cells via the Schaffer collateral and [[commissural fiber]]s from the [[contralateral]] hippocampus as well.


==Function==
==Function==
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===Long-term Potentiation===
===Long-term Potentiation===
[[Long-term potentiation|Long-term potentiation (LTP)]] in the [[hippocampal formation]] is an example model for [[neural plasticity]].<ref name="Komai">Komai S, Matsuyama T, Matsumoto K, Kato K, Kobayashi M, Imamura K, Yoshida S, Ugawa S & Shiosaka S (2000). [[OPN5|Neuropsin]] regulates an early phase of Schaffer-collateral [[long-term potentiation]] in the [[murine]] [[hippocampus]]. ''European Journal of Neurosience''. 12:1479-1486</ref> Schaffer collateral synapses have been used as a sample synapse, a typical [[excitatory]] [[glutamatergic]] [[synapse]] in the [[Cerebral cortex|cortex]] that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well. LTPs are involved in how people store information and how they retrieve information and involve networks of memories that are involved in facts and in [[emotion]]s as well because the [[hippocampus]] is the part of the [[limbic system]] connected to the [[amygdala]].
[[Long-term potentiation|Long-term potentiation (LTP)]] in the [[hippocampal formation]] is an example model for [[neural plasticity]].<ref name="Komai">{{cite journal |last1=Komai |first1=Shoji |last2=Matsuyama |first2=Tomohiro |last3=Matsumoto |first3=Kazumasa |last4=Kato |first4=Keiko |last5=Kobayashi |first5=Masayuki |last6=Imamura |first6=Kazuyuki |last7=Yoshida |first7=Shigetaka |last8=Ugawa |first8=Shinya |last9=Shiosaka |first9=Sadao |title=Neuropsin regulates an early phase of Schaffer-collateral long-term potentiation in the murine hippocampus |journal=European Journal of Neuroscience |date=April 2000 |volume=12 |issue=4 |pages=1479–1486 |doi=10.1046/j.1460-9568.2000.00035.x |pmid=10762375}}</ref> Schaffer collateral synapses have been used as a sample synapse, a typical [[excitatory]] [[glutamatergic]] [[synapse]] in the [[Cerebral cortex|cortex]] that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well. LTPs are involved in how people store information and how they retrieve information and involve networks of memories that are involved in facts and in [[emotion]]s as well because the [[hippocampus]] is the part of the [[limbic system]] connected to the [[amygdala]].


LTP in the hippocampus is an important model for [[neural plasticity]] that contributes to learning and memory.<ref name="Komai">Komai S, Matsuyama T, Matsumoto K, Kato K, Kobayashi M, Imamura K, Yoshida S, Ugawa S, Shiosaka S. (2000). [[OPN5|Neuropsin]] regulates an early phase of Schaffer-collateral long-term potentiation in the murin hippocampus. ''European Journal of Neuroscience''. 12: 1479-1486.</ref> The study on Schaffer collateral is important because the Schaffer collaterals are the [[axon]]s of the [[neuron]]s in the CA3 regions of the hippocampus that form [[synapse]]s in the CA1 regions.
LTP in the hippocampus is an important model for [[neural plasticity]] that contributes to learning and memory.<ref name="Komai"/> The study on Schaffer collateral is important because the Schaffer collaterals are the [[axon]]s of the [[neuron]]s in the CA3 regions of the hippocampus that form [[synapse]]s in the CA1 regions.


The hippocampus is a part of the [[feedback]] process that sends signals to stop [[cortisol]] production. Thus, a damaged hippocampus can cause [[memory loss]] and inability of [[cognitive function]]. Furthermore, as the hippocampus is the region controlling learning and memory processes, the research on Schaffer collaterals may help to find treatments for [[disease]]s related to the hippocampus or its neural processing pathways such as [[Alzheimer's disease]], a [[neurodegenerative disorder]].
The hippocampus is a part of the [[feedback]] process that sends signals to stop [[cortisol]] production. Thus, a damaged hippocampus can cause [[memory loss]] and inability of [[cognitive function]]. Furthermore, as the hippocampus is the region controlling learning and memory processes, the research on Schaffer collaterals may help to find treatments for [[disease]]s related to the hippocampus or its neural processing pathways such as [[Alzheimer's disease]], a [[neurodegenerative disorder]].


[[Long-term potentiation]] (LTP) of [[synaptic strength]] at Schaffer collateral [[synapse]]s has largely been attributed to changes in the number and biophysical properties of [[AMPA receptor]]s (AMPARs).<ref name="Lin">Lin MT, Lujan R, Watanabe M, Adelman JP & Maylie J (2007). SK2 channel plasticity contributes to LTP at Schaffer collateral-CA1 synapses. ''Nature Neuroscience''. 11(2): 170-176</ref> [[OPN5|Neuropsin]] has a regulatory effect on Schaffer collateral LTP in the rat hippocampus<ref name="Komai">Komai S, Matsuyama T, Matsumoto K, Kato K, Kobayashi M, Imamura K, Yoshida S, Ugawa S & Shiosaka S. (2000). [[OPN5|Neuropsin]] regulates an early phase of Schaffer-collateral long-term potentiation in the [[murine]] [[hippocampus]]. Eu. Neuroscience Association. 12: 1479-1486</ref>
[[Long-term potentiation]] (LTP) of [[synaptic strength]] at Schaffer collateral [[synapse]]s has largely been attributed to changes in the number and biophysical properties of [[AMPA receptor]]s (AMPARs).<ref name="Lin">{{cite journal |last1=Lin |first1=Mike T |last2=Luján |first2=Rafael |last3=Watanabe |first3=Masahiko |last4=Adelman |first4=John P |last5=Maylie |first5=James |title=SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapses |journal=Nature Neuroscience |date=20 January 2008 |volume=11 |issue=2 |pages=170–177 |doi=10.1038/nn2041 |pmid=18204442 |pmc=2613806}}</ref> [[OPN5|Neuropsin]] has a regulatory effect on Schaffer collateral LTP in the rat hippocampus.<ref name="Komai"/>


The functional hippocampus needs to store long-term memories. Once the memories are stored, they remain stored for a long time. Long-term changes in [[synaptic efficacy]] in the hippocampus can be induced by different patterns of stimulation generating [[presynaptic]] and [[postsynaptic]] [[depolarization]]<ref name="Hoffman">Hoffman DA, Sprengel R & Sakmann B (2002). Molecular [[dissection]] of hippocampal theta-burst pairing potentiation. PNAS.99 (11): 7740-7745</ref> The theta burst stimulation of Schaffer collaterals can be sufficient to induce LTP by promoting the formation of filamentous [[actin]] in CA1 [[dendrite]]s.<ref name="Meighan">Meighan PC, Meighan SE, Davis CJ, Wright JW & Harding JW (2007). Effects of matrix [[metalloproteinase]] [[Reaction inhibitor|inhibition]] on short-and long-term plasticity of Schaffer collateral/CA1 synapses. ''Journal of Neurochemistry''. 102:2085-2096</ref> Within the [[mammalian brain]], some patterns of synaptic activity produce long-term potentiation (LTP) which is a long-lasting increase in [[synaptic strength]] and [[long-term depression]] (LTD) which is a long-lasting decrease in synaptic strength.
The functional hippocampus needs to store long-term memories. Once the memories are stored, they remain stored for a long time. Long-term changes in [[synaptic efficacy]] in the hippocampus can be induced by different patterns of stimulation generating [[presynaptic]] and [[postsynaptic]] [[depolarization]]<ref name="Hoffman">{{cite journal |last1=Hoffman |first1=D. A. |last2=Sprengel |first2=R. |last3=Sakmann |first3=B. |title=Molecular dissection of hippocampal theta-burst pairing potentiation |journal=Proceedings of the National Academy of Sciences |date=21 May 2002 |volume=99 |issue=11 |pages=7740–7745 |doi=10.1073/pnas.092157999 |pmid=12032353 |pmc=124338}}</ref> The theta burst stimulation of Schaffer collaterals can be sufficient to induce LTP by promoting the formation of filamentous [[actin]] in CA1 [[dendrite]]s.<ref name="Meighan">{{cite journal |last1=Meighan |first1=Peter C. |last2=Meighan |first2=Starla E. |last3=Davis |first3=Christopher J. |last4=Wright |first4=John W. |last5=Harding |first5=Joseph W. |title=Effects of matrix metalloproteinase inhibition on short- and long-term plasticity of schaffer collateral/CA1 synapses |journal=Journal of Neurochemistry |date=September 2007 |volume=102 |issue=6 |pages=2085–2096 |doi=10.1111/j.1471-4159.2007.04682.x |doi-access=free |pmid=17587312}}</ref> Within the [[mammalian brain]], some patterns of synaptic activity produce long-term potentiation (LTP) which is a long-lasting increase in [[synaptic strength]] and [[long-term depression]] (LTD) which is a long-lasting decrease in synaptic strength.


====LTP at Schaffer collateral-CA1 synapses and "SK2 channel plasticity"====
====LTP at Schaffer collateral-CA1 synapses and "SK2 channel plasticity"====
Long-term plasticity in synapses of the [[hippocampus]] can be induced by different patterns of stimulation generating pre- and post-synaptic [[depolarization]]. These synaptic changes can clearly lead to modification in circuit function and to behavioral plasticity. Some patterns of synaptic activity produce an extensive increase in synaptic strength, also known as Long-Term Potentiation (LTP). In the hippocampus, LTP at Schaffer collateral-CA1 modulates the biophysical properties of AMPA receptors. Moreover, [[SK channel|SK2]], small-conductance Ca2+-activated [[K+ channel]], changes the shape of [[excitatory postsynaptic potential]]s (EPSPs) by coupling with N-methyl D-aspartate receptors ([[NMDA receptor]]s). The research by Lin MT, ''et al.'' was designed to investigate whether [[SK channel|SK2 channels]] participate in synaptic changes when an activity-dependent decrease contributes to LTP.<ref name ="Lin MT">Lin MT, Lujuan R, Watanabe M, Adelman JP, Maylie J (2008). SK2 channel plasticity contributes to LTP at Schaffer collateral-CA1 synapses. ''Nature''. 11 (2): 170-177</ref>
Long-term plasticity in synapses of the [[hippocampus]] can be induced by different patterns of stimulation generating pre- and post-synaptic [[depolarization]]. These synaptic changes can clearly lead to modification in circuit function and to behavioral plasticity. Some patterns of synaptic activity produce an extensive increase in synaptic strength, also known as Long-Term Potentiation (LTP). In the hippocampus, LTP at Schaffer collateral-CA1 modulates the biophysical properties of AMPA receptors. Moreover, [[SK channel|SK2]], small-conductance Ca2+-activated [[K+ channel]], changes the shape of [[excitatory postsynaptic potential]]s (EPSPs) by coupling with N-methyl D-aspartate receptors ([[NMDA receptor]]s). The research by Lin MT, ''et al.'' was designed to investigate whether [[SK channel|SK2 channels]] participate in synaptic changes when an activity-dependent decrease contributes to LTP.<ref name="Lin"/>


[[SK channel|SK2 channels]] are [[ion channel]]s that are activated by an increasing in the concentration of intracellular [[calcium]] and as a result of allowing K+ cation to cross the cell membrane. The double [[immunogold labeling]] identified that SK2 channels and NMDA cohabit within the [[postsynaptic density]] (PSD) of CA1 regions of the [[hippocampus]]. The authors used theta-burst pairing (TBP) to produce a rapid potentiation of [[synaptic strength]] and to evoke LTP that is induced simultaneously but whose expression levels vary inversely over time, and the result of the TBP induction was compared to the control group. The result showed that the TBP induction of LTP significantly increased [[EPSP]]s level. When the stimulus strength was reduced below the [[action potential]] threshold, [[apamin]], a [[neurotoxin]], was added to assess the contribution of SK2 activity to EPSPs. It resulted in an increase in the level of EPSPs with blockage of SK2 channels. The TBP induction of LTP abolishes SK2 channel contribution to EPSPs. When the induction of chemical LTP was applied, immunoparticles for SK2 were not found within the [[postsynaptic density|PSD]] of asymmetrical synapses. However, the SK2 immunoparticles were observed within [[intracellular]] [[biological membrane|membrane]]s. The activation of [[protein kinase A]] (PKA) downregulates the surface expression of SK2 because PKA regulates the surface expression of [[AMPA receptor]]s, a non-NMDA-type [[ionotropic]] [[transmembrane]] receptor, in the hippocampus. Therefore, PKA decreases the activity of LTP-dependent of SK2 channels.[[Schaffer collateral#Long-term plasticity]]
[[SK channel|SK2 channels]] are [[ion channel]]s that are activated by an increasing in the concentration of intracellular [[calcium]] and as a result of allowing K+ cation to cross the cell membrane. The double [[immunogold labeling]] identified that SK2 channels and NMDA cohabit within the [[postsynaptic density]] (PSD) of CA1 regions of the [[hippocampus]]. The authors used theta-burst pairing (TBP) to produce a rapid potentiation of [[synaptic strength]] and to evoke LTP that is induced simultaneously but whose expression levels vary inversely over time, and the result of the TBP induction was compared to the control group. The result showed that the TBP induction of LTP significantly increased [[EPSP]]s level. When the stimulus strength was reduced below the [[action potential]] threshold, [[apamin]], a [[neurotoxin]], was added to assess the contribution of SK2 activity to EPSPs. It resulted in an increase in the level of EPSPs with blockage of SK2 channels. The TBP induction of LTP abolishes SK2 channel contribution to EPSPs. When the induction of chemical LTP was applied, immunoparticles for SK2 were not found within the [[postsynaptic density|PSD]] of asymmetrical synapses. However, the SK2 immunoparticles were observed within [[intracellular]] [[biological membrane|membrane]]s. The activation of [[protein kinase A]] (PKA) downregulates the surface expression of SK2 because PKA regulates the surface expression of [[AMPA receptor]]s, a non-NMDA-type [[ionotropic]] [[transmembrane]] receptor, in the hippocampus. Therefore, PKA decreases the activity of LTP-dependent of SK2 channels.[[Schaffer collateral#Long-term plasticity]]


===Short-term plasticity===
===Short-term plasticity===
Short-term synaptic plasticity undergoes important age-dependent changes that have crucial implications during the development of the [[nervous system]]<ref name="Schiess">Schiess ARB, Scullin C & Partridge LD (2010). Maturation of Schaffer collateral synapses generates a [[phenotype]] of unreliable basal evoked release and very reliable facilitated release. ''Eu. Journal of Neuroscience''. 31: 1377-1387</ref>
Short-term synaptic plasticity undergoes important age-dependent changes that have crucial implications during the development of the [[nervous system]]<ref name="Schiess">{{cite journal |last1=Schiess |first1=Adrian R. B. |last2=Scullin |first2=Chessa |last3=Donald Partridge |first3=L. |title=Maturation of Schaffer collateral synapses generates a phenotype of unreliable basal evoked release and very reliable facilitated release |journal=European Journal of Neuroscience |date=April 2010 |volume=31 |issue=8 |pages=1377–1387 |doi=10.1111/j.1460-9568.2010.07180.x |pmid=20384768 |pmc=3575738}}</ref>


==Vesicular release at "Schaffer Collateral"==
==Vesicular release at "Schaffer Collateral"==
{{Inappropriate tone|section|date=March 2013}}
{{Inappropriate tone|section|date=March 2013}}
The way [[transmitter]] release works is every terminal at every pre-synapse in your brain has a large pool of [[vesicle (biology and chemistry)|vesicles]] that are filled with [[glutamate]] and that can be used to release a [[neurotransmitter]]. However, in any given time, most of them are not being used. This is known as the reserve pool. The readily recyclable pool or rapidly recycling pool is 10% of what is being used all the time. When a [[transmitter]] is released, a vesicle does not just get thrown away. The vesicles are actually resealed, and they get recycled back around and stuck preferentially back into the rapidly recycling pool, not the reserve pool, so they can be used again. Most of the vesicles in the reserve pool are released only when it is activated at the maximum strength, as by [[Polarization (electrochemistry)|polarizing]] them with high [[potassium]] or by driving with the high frequency of [[action potential]]s. The little recycling vesicles can't keep up. Then, signals tell the reserve pool to release what it stores in itself. The acting zone of the reserve pool has its certain length with so many docking sites. The vesicles have to dock to the sealed complex. They have to bind to the right place. When [[calcium]] comes in, it binds, releases the vesicle, and opens up to release a [[neurotransmitter]]. Therefore, how fast [[endocytosis]] occurs means how fast the vesicles get back into the recycling pool.<ref name="Stanton">Stanton PK, Winterer J, Zhang X & Muller W (2005). Imaging LTP of presynaptic release of FM1-43 [http://student.biology.arizona.edu/honors2004/group04/fm143.html] from the rapidly recycling vesicle pool of Schaffer collateral-CA1 synapses in rat hippocampal slices. ''European Journal of Neuroscience''. 22:2451-2461</ref>
The way [[transmitter]] release works is every terminal at every pre-synapse in your brain has a large pool of [[vesicle (biology and chemistry)|vesicles]] that are filled with [[glutamate]] and that can be used to release a [[neurotransmitter]]. However, in any given time, most of them are not being used. This is known as the reserve pool. The readily recyclable pool or rapidly recycling pool is 10% of what is being used all the time. When a [[transmitter]] is released, a vesicle does not just get thrown away. The vesicles are actually resealed, and they get recycled back around and stuck preferentially back into the rapidly recycling pool, not the reserve pool, so they can be used again. Most of the vesicles in the reserve pool are released only when it is activated at the maximum strength, as by [[Polarization (electrochemistry)|polarizing]] them with high [[potassium]] or by driving with the high frequency of [[action potential]]s. The little recycling vesicles can't keep up. Then, signals tell the reserve pool to release what it stores in itself. The acting zone of the reserve pool has its certain length with so many docking sites. The vesicles have to dock to the sealed complex. They have to bind to the right place. When [[calcium]] comes in, it binds, releases the vesicle, and opens up to release a [[neurotransmitter]]. Therefore, how fast [[endocytosis]] occurs means how fast the vesicles get back into the recycling pool.<ref name="Stanton">{{cite journal |last1=Stanton |first1=Patric K. |last2=Winterer |first2=Jochen |last3=Zhang |first3=Xiao-lei |last4=Müller |first4=Wolfgang |title=Imaging LTP of presynaptic release of FM1-43 from the rapidly recycling vesicle pool of Schaffer collateral-CA1 synapses in rat hippocampal slices |journal=European Journal of Neuroscience |date=November 2005 |volume=22 |issue=10 |pages=2451–2461 |doi=10.1111/j.1460-9568.2005.04437.x |pmid=16307588}}</ref>


Multivesicular release (MVR) occurs at Schaffer collateral-CA1 synapses when P is elevated by [[neural facilitation|facilitation]] and that MVR may be a phenomenon common to many synapses throughout the [[central nervous system]].<ref name ="Christie">Christie JM and Jahr CE (2006). Multivesicular Release at Schaffer Collateral-CA1 Hippocampal synapses. ''The Journal of Neuroscience''. 26(1):210-216</ref>
Multivesicular release (MVR) occurs at Schaffer collateral-CA1 synapses when P is elevated by [[neural facilitation|facilitation]] and that MVR may be a phenomenon common to many synapses throughout the [[central nervous system]].<ref name ="Christie">{{cite journal |last1=Christie |first1=J. M. |last2=Jahr |first2=CE |title=Multivesicular release at Schaffer collateral-CA1 hippocampal synapses |journal=Journal of Neuroscience |date=4 January 2006 |volume=26 |issue=1 |pages=210–216 |doi=10.1523/JNEUROSCI.4307-05.2006 |pmid=16399689 |pmc=2670931}}</ref>


==References==
==References==

Revision as of 22:16, 2 September 2018

Schaffer collaterals are axon collaterals given off by CA3 pyramidal cells in the hippocampus. These collaterals project to area CA1 of the hippocampus[1] and are an integral part of memory formation and the emotional network of the Papez circuit, and of the hippocampal trisynaptic loop. It is one of the most studied synapses in the world and named after the Hungarian anatomist-neurologist Károly Schaffer.

As a part of the hippocampal structures, Schaffer collaterals develop the limbic system, which plays a critical role in the aspects of learning and memory. The signals of information from the contralateral CA3 region leave via the Schaffer collateral pathways for the CA1 pyramidal neurons. Mature synapses contain fewer Schaffer collateral branches than those synapses that are not fully developed.[2] Many scientists try to use the Schaffer collateral synapse as a sample synapse, a typical excitatory glutamatergic synapse in the cortex that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well and to develop medication and treatment to cure the chronic diseases, such as dementia and Alzheimer's disease. Moreover, they believe that studying the Schaffer collateral can provide a whole range of understanding how Schaffer collaterals allow us to intervene with drug-treatments and with electrical-stimulation so that the quality of human experience can be improved.

Development

"Schaffer collateral is the conductor of the orchestra, but not the actual instrument that plays the music" - Dr. Patrick K. Stanton [1].

An individual needs the functional hippocampus to store long-term memories as synaptic plasticity in terms of storing information. Once those memories are stored, they remain stored in very long time. However, they slowly fade away, which means that there are some roles for the hippocampus when talking to the neocortex in order to prevent diminishing those memories away. It is clear that whatever plastic changes occurring in the hippocampus involve in directing the process by which memories get stored.

The Schaffer collateral is involved in activity-dependent plasticity and the information processes that always are processed through the hippocampus all the time. The Schaffer collateral clearly affects whether the target cells fire action potentials or not. However, at the same time, it is triggering the process that takes much longer whereby some synapses get stronger and some get weaker, and overall the patterns of synaptic strength of the network all evolve over time.

Moreover, Schaffer collateral axons develop excitatory synapses that are scattered over the dendritic arborization[3] of hippocampal CA1 pyramidal neurons.[4] In the early stage of long-term potentiation, Schaffer collaterals release glutamate that binds to AMPA receptors of CA1-dendrites. The process of developing a network of CA3-to-CA1 recurrent excitatory glutamatergic synapses alters the frequency of spontaneous action potentials in Schaffer collaterals. By adulthood, CA3 recurrent network activity is reduced, the frequency of spontaneous action potentials is decreased in Schaffer collaterals, and a single release locus synapse with one dendritic spine on a given CA1 pyramidal neuron can be developed by Schaffer collateral axons.[2]

Location

The Schaffer collateral is located between the CA3 region and CA1 region in the hippocampus. Schaffer collaterals are the axons of pyramidal cells that connect two neurons (CA3 and CA1) and transfer information from CA3 to CA1.[5][6] The entorhinal cortex sends the main input to the dentate gyrus (perforant pathway). From the granule cells of the dentate gyrus, connections are made to the CA3 regions of the hippocampus via mossy fibers. CA3 sends the information signals to CA1 pyramidal cells via the Schaffer collateral and commissural fibers from the contralateral hippocampus as well.

Function

Throughout the memory process in the hippocampus, Schaffer collaterals seem not to play a major role in the formation of actual memory, but it is clear that Schaffer collaterals assist the activity-dependent plasticity and the information processes that are always altered over the course of memory development in the hippocampus. Schaffer collaterals alter the development of the limbic system that is critical for learning and memory. The contralateral CA3 region sends information through Schaffer collateral to the CA1 pyramidal neurons.

Schaffer collateral and hippocampal synaptic plasticity

Plastic changes occurring in the hippocampus are involved in directing the process by which memories get stored. Schaffer collaterals affect the hippocampus to develop short (Short-term Plasticity) and long term synaptic plasticity (Long-term Plasticity) in terms of storing information and changing in the efficiency of synaptic transmission following previous synaptic activity.

Long-term Potentiation

Long-term potentiation (LTP) in the hippocampal formation is an example model for neural plasticity.[7] Schaffer collateral synapses have been used as a sample synapse, a typical excitatory glutamatergic synapse in the cortex that has very well been studied in order to try to identify the rules of both the patterns of stimulation in electrical rules and the chemical mechanisms by which synapses get persistently stronger and which synapses get persistently weaker as well. LTPs are involved in how people store information and how they retrieve information and involve networks of memories that are involved in facts and in emotions as well because the hippocampus is the part of the limbic system connected to the amygdala.

LTP in the hippocampus is an important model for neural plasticity that contributes to learning and memory.[7] The study on Schaffer collateral is important because the Schaffer collaterals are the axons of the neurons in the CA3 regions of the hippocampus that form synapses in the CA1 regions.

The hippocampus is a part of the feedback process that sends signals to stop cortisol production. Thus, a damaged hippocampus can cause memory loss and inability of cognitive function. Furthermore, as the hippocampus is the region controlling learning and memory processes, the research on Schaffer collaterals may help to find treatments for diseases related to the hippocampus or its neural processing pathways such as Alzheimer's disease, a neurodegenerative disorder.

Long-term potentiation (LTP) of synaptic strength at Schaffer collateral synapses has largely been attributed to changes in the number and biophysical properties of AMPA receptors (AMPARs).[8] Neuropsin has a regulatory effect on Schaffer collateral LTP in the rat hippocampus.[7]

The functional hippocampus needs to store long-term memories. Once the memories are stored, they remain stored for a long time. Long-term changes in synaptic efficacy in the hippocampus can be induced by different patterns of stimulation generating presynaptic and postsynaptic depolarization[9] The theta burst stimulation of Schaffer collaterals can be sufficient to induce LTP by promoting the formation of filamentous actin in CA1 dendrites.[10] Within the mammalian brain, some patterns of synaptic activity produce long-term potentiation (LTP) which is a long-lasting increase in synaptic strength and long-term depression (LTD) which is a long-lasting decrease in synaptic strength.

LTP at Schaffer collateral-CA1 synapses and "SK2 channel plasticity"

Long-term plasticity in synapses of the hippocampus can be induced by different patterns of stimulation generating pre- and post-synaptic depolarization. These synaptic changes can clearly lead to modification in circuit function and to behavioral plasticity. Some patterns of synaptic activity produce an extensive increase in synaptic strength, also known as Long-Term Potentiation (LTP). In the hippocampus, LTP at Schaffer collateral-CA1 modulates the biophysical properties of AMPA receptors. Moreover, SK2, small-conductance Ca2+-activated K+ channel, changes the shape of excitatory postsynaptic potentials (EPSPs) by coupling with N-methyl D-aspartate receptors (NMDA receptors). The research by Lin MT, et al. was designed to investigate whether SK2 channels participate in synaptic changes when an activity-dependent decrease contributes to LTP.[8]

SK2 channels are ion channels that are activated by an increasing in the concentration of intracellular calcium and as a result of allowing K+ cation to cross the cell membrane. The double immunogold labeling identified that SK2 channels and NMDA cohabit within the postsynaptic density (PSD) of CA1 regions of the hippocampus. The authors used theta-burst pairing (TBP) to produce a rapid potentiation of synaptic strength and to evoke LTP that is induced simultaneously but whose expression levels vary inversely over time, and the result of the TBP induction was compared to the control group. The result showed that the TBP induction of LTP significantly increased EPSPs level. When the stimulus strength was reduced below the action potential threshold, apamin, a neurotoxin, was added to assess the contribution of SK2 activity to EPSPs. It resulted in an increase in the level of EPSPs with blockage of SK2 channels. The TBP induction of LTP abolishes SK2 channel contribution to EPSPs. When the induction of chemical LTP was applied, immunoparticles for SK2 were not found within the PSD of asymmetrical synapses. However, the SK2 immunoparticles were observed within intracellular membranes. The activation of protein kinase A (PKA) downregulates the surface expression of SK2 because PKA regulates the surface expression of AMPA receptors, a non-NMDA-type ionotropic transmembrane receptor, in the hippocampus. Therefore, PKA decreases the activity of LTP-dependent of SK2 channels.Schaffer collateral#Long-term plasticity

Short-term plasticity

Short-term synaptic plasticity undergoes important age-dependent changes that have crucial implications during the development of the nervous system[2]

Vesicular release at "Schaffer Collateral"

The way transmitter release works is every terminal at every pre-synapse in your brain has a large pool of vesicles that are filled with glutamate and that can be used to release a neurotransmitter. However, in any given time, most of them are not being used. This is known as the reserve pool. The readily recyclable pool or rapidly recycling pool is 10% of what is being used all the time. When a transmitter is released, a vesicle does not just get thrown away. The vesicles are actually resealed, and they get recycled back around and stuck preferentially back into the rapidly recycling pool, not the reserve pool, so they can be used again. Most of the vesicles in the reserve pool are released only when it is activated at the maximum strength, as by polarizing them with high potassium or by driving with the high frequency of action potentials. The little recycling vesicles can't keep up. Then, signals tell the reserve pool to release what it stores in itself. The acting zone of the reserve pool has its certain length with so many docking sites. The vesicles have to dock to the sealed complex. They have to bind to the right place. When calcium comes in, it binds, releases the vesicle, and opens up to release a neurotransmitter. Therefore, how fast endocytosis occurs means how fast the vesicles get back into the recycling pool.[11]

Multivesicular release (MVR) occurs at Schaffer collateral-CA1 synapses when P is elevated by facilitation and that MVR may be a phenomenon common to many synapses throughout the central nervous system.[12]

References

  1. ^ Vago, David R.; Kesner, Raymond P. (June 2008). "Disruption of the direct perforant path input to the CA1 subregion of the dorsal hippocampus interferes with spatial working memory and novelty detection". Behavioural Brain Research. 189 (2): 273–283. doi:10.1016/j.bbr.2008.01.002. PMC 2421012. PMID 18313770.
  2. ^ a b c Schiess, Adrian R. B.; Scullin, Chessa; Donald Partridge, L. (April 2010). "Maturation of Schaffer collateral synapses generates a phenotype of unreliable basal evoked release and very reliable facilitated release". European Journal of Neuroscience. 31 (8): 1377–1387. doi:10.1111/j.1460-9568.2010.07180.x. PMC 3575738. PMID 20384768.
  3. ^ "arborization". The Free Dictionary.
  4. ^ Smith, M. A; Ellis-Davies, G. C R; Magee, J. C (21 February 2003). "Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons". The Journal of Physiology. 548 (1): 245–258. doi:10.1113/jphysiol.2002.036376. PMC 2342790. PMID 12598591.
  5. ^ Lebeau, Geneviève; DesGroseillers, Luc; Sossin, Wayne; Lacaille, Jean-Claude (2011). "mRNA binding protein staufen 1-dependent regulation of pyramidal cell spine morphology via NMDA receptor-mediated synaptic plasticity". Molecular Brain. 4 (1): 22. doi:10.1186/1756-6606-4-22. PMC 3118231. PMID 21635779.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Arrigoni, Elda; Greene, Robert W (May 2004). "Schaffer collateral and perforant path inputs activate different subtypes of NMDA receptors on the same CA1 pyramidal cell". British Journal of Pharmacology. 142 (2): 317–322. doi:10.1038/sj.bjp.0705744. PMC 1574942. PMID 15155538.
  7. ^ a b c Komai, Shoji; Matsuyama, Tomohiro; Matsumoto, Kazumasa; Kato, Keiko; Kobayashi, Masayuki; Imamura, Kazuyuki; Yoshida, Shigetaka; Ugawa, Shinya; Shiosaka, Sadao (April 2000). "Neuropsin regulates an early phase of Schaffer-collateral long-term potentiation in the murine hippocampus". European Journal of Neuroscience. 12 (4): 1479–1486. doi:10.1046/j.1460-9568.2000.00035.x. PMID 10762375.
  8. ^ a b Lin, Mike T; Luján, Rafael; Watanabe, Masahiko; Adelman, John P; Maylie, James (20 January 2008). "SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapses". Nature Neuroscience. 11 (2): 170–177. doi:10.1038/nn2041. PMC 2613806. PMID 18204442.
  9. ^ Hoffman, D. A.; Sprengel, R.; Sakmann, B. (21 May 2002). "Molecular dissection of hippocampal theta-burst pairing potentiation". Proceedings of the National Academy of Sciences. 99 (11): 7740–7745. doi:10.1073/pnas.092157999. PMC 124338. PMID 12032353.
  10. ^ Meighan, Peter C.; Meighan, Starla E.; Davis, Christopher J.; Wright, John W.; Harding, Joseph W. (September 2007). "Effects of matrix metalloproteinase inhibition on short- and long-term plasticity of schaffer collateral/CA1 synapses". Journal of Neurochemistry. 102 (6): 2085–2096. doi:10.1111/j.1471-4159.2007.04682.x. PMID 17587312.
  11. ^ Stanton, Patric K.; Winterer, Jochen; Zhang, Xiao-lei; Müller, Wolfgang (November 2005). "Imaging LTP of presynaptic release of FM1-43 from the rapidly recycling vesicle pool of Schaffer collateral-CA1 synapses in rat hippocampal slices". European Journal of Neuroscience. 22 (10): 2451–2461. doi:10.1111/j.1460-9568.2005.04437.x. PMID 16307588.
  12. ^ Christie, J. M.; Jahr, CE (4 January 2006). "Multivesicular release at Schaffer collateral-CA1 hippocampal synapses". Journal of Neuroscience. 26 (1): 210–216. doi:10.1523/JNEUROSCI.4307-05.2006. PMC 2670931. PMID 16399689.
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