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Silent synapse
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==Competing Hypotheses== The characterization of silent synapses is an ongoing field of research and there are many things about them that are not yet known. Some of what is currently accepted about the properties of silent synapses may still prove to be incorrect in whole or in part. Some controversies about silent synapses have however, been settled. For example, until recently, there were four competing hypotheses for the mechanisms of synapse silence:<ref name="Voronin 2004">{{cite journal | vauthors = Voronin LL, Cherubini E | title = 'Deaf, mute and whispering' silent synapses: their role in synaptic plasticity | journal = The Journal of Physiology | volume = 557 | issue = Pt 1 | pages = 3β12 | date = May 2004 | pmid = 15034124 | pmc = 1665055 | doi = 10.1113/jphysiol.2003.058966 }}</ref> *The "whispering synapse" hypothesis: **A synapse that releases glutamate more slowly than normal, thus activating only high affinity NMDA receptors, but not low affinity AMPA receptors *The "low Pr" synapse hypothesis: **A synapse that is not technically silent, but appears to be so, because it has such a low presynaptic probability of release that it rarely is activated. *The "glutamate spillover" hypothesis: **A synapse that does not release its own presynaptic glutamate, but in which the postsynapse detects low concentrations of glutamate "spilling over" from neighboring synapses. Only the high affinity NMDARs, but not the low affinity AMPARs can detect this low level of glutamate *The "lack of AMPA receptor" hypothesis **A synapse that lacks postsynaptic AMPA receptors All four of these hypotheses had their adherents, but the first three were largely ruled out as a mechanism for synapse silence by work published before 2008.<ref name="Montgomery 2002">{{cite journal |author-link=Johanna Montgomery |vauthors=Montgomery JM, Pavlidis P, Madison DV |date=March 2001 |title=Pair recordings reveal all-silent synaptic connections and the postsynaptic expression of long-term potentiation |journal=Neuron |volume=29 |issue=3 |pages=691β701 |doi=10.1016/S0896-6273(01)00244-6 |pmid=11301028 |doi-access=free}}</ref> However, recent experiments have clearly established that silent synapses can be observed at brainstem synapses bearing postsynaptic AMPA receptors.<ref name="Balland 2008">{{cite journal | vauthors = Balland B, Lachamp P, Kessler JP, Tell F | title = Silent synapses in developing rat nucleus tractus solitarii have AMPA receptors | journal = The Journal of Neuroscience | volume = 28 | issue = 18 | pages = 4624β34 | date = April 2008 | pmid = 18448639 | pmc = 6670440| doi = 10.1523/JNEUROSCI.5355-07.2008 }}</ref> This study favors the glutamate spillover hypothesis by showing that at silent synapses the glutamate concentration is reduced. At least, this study indicates that the popular hypothesis of the postsynaptic silent synapses does not apply in all systems.
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