Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-15917-1
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dc.titleBidirectional modulation of hippocampal synaptic plasticity by Dopaminergic D4-receptors in the CA1 area of hippocampus
dc.contributor.authorNavakkode S.
dc.contributor.authorChew K.C.M.
dc.contributor.authorTay S.J.N.
dc.contributor.authorLin Q.
dc.contributor.authorBehnisch T.
dc.contributor.authorSoong T.W.
dc.date.accessioned2020-09-09T03:16:43Z
dc.date.available2020-09-09T03:16:43Z
dc.date.issued2017
dc.identifier.citationNavakkode S., Chew K.C.M., Tay S.J.N., Lin Q., Behnisch T., Soong T.W. (2017). Bidirectional modulation of hippocampal synaptic plasticity by Dopaminergic D4-receptors in the CA1 area of hippocampus. Scientific Reports 7 (1) : 15571. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-15917-1
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175093
dc.description.abstractLong-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP. This effect was dependent on protein synthesis, activation of NMDA-receptors and CaMKII. We also show that GABAA-receptor mediated mechanisms are involved in the enhancement of late-LTP. We could show that short-term plasticity and baseline synaptic transmission were unaffected by D4R inhibition. On the other hand, antagonizing D4R prevented both early and late forms of LTD, showing that activation of D4Rs triggered a dual function. Synaptic tagging experiments on LTD showed that D4Rs act as plasticity related proteins rather than the setting of synaptic tags. D4R activation by PD 168077 induced a slow-onset depression that was protein synthesis, NMDAR and CaMKII dependent. The D4 receptors, thus exert a bidirectional modulation of CA1 pyramidal neurons by restricting synaptic strengthening and facilitating synaptic weakening. © 2017 The Author(s).
dc.sourceUnpaywall 20200831
dc.subjectbenzamide derivative
dc.subjectcalcium calmodulin dependent protein kinase II
dc.subjectdopamine 4 receptor
dc.subjectGrin3a protein, rat
dc.subjectmembrane protein
dc.subjectN-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide
dc.subjectpiperazine derivative
dc.subjectanimal
dc.subjectantagonists and inhibitors
dc.subjectdopaminergic nerve cell
dc.subjectdrug effect
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjecthippocampal CA1 region
dc.subjecthippocampus
dc.subjecthuman
dc.subjectlong term depression
dc.subjectlong term potentiation
dc.subjectnerve cell network
dc.subjectnerve cell plasticity
dc.subjectpathophysiology
dc.subjectphysiology
dc.subjectprotein synthesis
dc.subjectrat
dc.subjectsynapse
dc.subjectsynaptic transmission
dc.subjectAnimals
dc.subjectBenzamides
dc.subjectCA1 Region, Hippocampal
dc.subjectCalcium-Calmodulin-Dependent Protein Kinase Type 2
dc.subjectDopaminergic Neurons
dc.subjectGene Expression Regulation
dc.subjectHippocampus
dc.subjectHumans
dc.subjectLong-Term Potentiation
dc.subjectLong-Term Synaptic Depression
dc.subjectMembrane Glycoproteins
dc.subjectNerve Net
dc.subjectNeuronal Plasticity
dc.subjectPiperazines
dc.subjectProtein Biosynthesis
dc.subjectRats
dc.subjectReceptors, Dopamine D4
dc.subjectSynapses
dc.subjectSynaptic Transmission
dc.typeArticle
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.1038/s41598-017-15917-1
dc.description.sourcetitleScientific Reports
dc.description.volume7
dc.description.issue1
dc.description.page15571
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