Effect of dopaminergic D1 receptors on plasticity is dependent of serotoninergic 5-HT1A receptors in L5-pyramidal neurons of the prefrontal cortex

PloS One
C N J MeunierP Fossier

Abstract

Major depression and schizophrenia are associated with dysfunctions of serotoninergic and dopaminergic systems mainly in the prefrontal cortex (PFC). Both serotonin and dopamine are known to modulate synaptic plasticity. 5-HT1A receptors (5-HT1ARs) and dopaminergic type D1 receptors are highly represented on dendritic spines of layer 5 pyramidal neurons (L5PyNs) in PFC. How these receptors interact to tune plasticity is poorly understood. Here we show that D1-like receptors (D1Rs) activation requires functional 5HT1ARs to facilitate LTP induction at the expense of LTD. Using 129/Sv and 5-HT1AR-KO mice, we recorded post-synaptic currents evoked by electrical stimulation in layer 2/3 after activation or inhibition of D1Rs. High frequency stimulation resulted in the induction of LTP, LTD or no plasticity. The D1 agonist markedly enhanced the NMDA current in 129/Sv mice and the percentage of L5PyNs displaying LTP was enhanced whereas LTD was reduced. In 5-HT1AR-KO mice, the D1 agonist failed to increase the NMDA current and orientated the plasticity towards L5PyNs displaying LTD, thus revealing a prominent role of 5-HT1ARs in dopamine-induced modulation of plasticity. Our data suggest that in pathological situation where 5-HT1ARs e...Continue Reading

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Citations

Feb 17, 2017·Frontiers in Synaptic Neuroscience·Claire N J MeunierPhilippe M Fossier
Mar 8, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lora L MartucciJosé-Manuel Cancela
Aug 21, 2018·Expert Opinion on Therapeutic Patents·Jakub StarońAndrzej J Bojarski
Jul 28, 2018·Molecular Neurobiology·Rémi ChaussenotCyrille Vaillend

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Methods Mentioned

BETA
biopsies

Software Mentioned

InVivoStat

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