Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-15917-1
Title: Bidirectional modulation of hippocampal synaptic plasticity by Dopaminergic D4-receptors in the CA1 area of hippocampus
Authors: Navakkode S. 
Chew K.C.M. 
Tay S.J.N.
Lin Q. 
Behnisch T.
Soong T.W. 
Keywords: benzamide derivative
calcium calmodulin dependent protein kinase II
dopamine 4 receptor
Grin3a protein, rat
membrane protein
N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide
piperazine derivative
animal
antagonists and inhibitors
dopaminergic nerve cell
drug effect
gene expression regulation
genetics
hippocampal CA1 region
hippocampus
human
long term depression
long term potentiation
nerve cell network
nerve cell plasticity
pathophysiology
physiology
protein synthesis
rat
synapse
synaptic transmission
Animals
Benzamides
CA1 Region, Hippocampal
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Dopaminergic Neurons
Gene Expression Regulation
Hippocampus
Humans
Long-Term Potentiation
Long-Term Synaptic Depression
Membrane Glycoproteins
Nerve Net
Neuronal Plasticity
Piperazines
Protein Biosynthesis
Rats
Receptors, Dopamine D4
Synapses
Synaptic Transmission
Issue Date: 2017
Citation: Navakkode 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
Abstract: Long-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).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/175093
ISSN: 20452322
DOI: 10.1038/s41598-017-15917-1
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