title: Effect of dopaminergic D1 receptors on plasticity is dependent of serotoninergic 5-HT1A receptors in L5-pyramidal neurons of the prefrontal cortex.
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 expression varies, dopaminergic treatment used for its ability to increase LTP could turn to be less and less effective.
authors.affiliation: Neuroscience Paris-Saclay Institute (NeuroPSI), UMR 8197 CNRS-Université Paris-Sud, Bâtiment 446, Université Paris-Sud, Orsay F-91405, France.
authors.forename: Claire Nicole Jeanne
authors.initials: CN
authors.lastname: Meunier
authors.affiliation: Université Paris Descartes, Laboratoire de Neuropharmacologie des addictions, INSERM U705 CNRS UMR 7157, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Callebert
authors.affiliation: Neuroscience Paris-Saclay Institute (NeuroPSI), UMR 8197 CNRS-Université Paris-Sud, Bâtiment 446, Université Paris-Sud, Orsay F-91405, France.
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Cancela
authors.affiliation: Neuroscience Paris-Saclay Institute (NeuroPSI), UMR 8197 CNRS-Université Paris-Sud, Bâtiment 446, Université Paris-Sud, Orsay F-91405, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fossier
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D017774:Long-Term Potentiation; D051379:Mice; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D044282:Receptor, Serotonin, 5-HT1A