title: Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning.
abstract: Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)2A receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. Here, we show that 5-HT2A receptor activation enhances NMDA transmission and gates the induction of temporal-dependent plasticity mediated by NMDA receptors at thalamocortical synapses in acute PFC slices. Expressing 5-HT2A receptors in the mediodorsal thalamus (presynaptic site) of 5-HT2A receptor-deficient mice, but not in the PFC (postsynaptic site), using a viral gene-delivery approach, rescued the otherwise absent potentiation of NMDA transmission, induction of temporal plasticity, and deficit in associative memory. These results provide, to our knowledge, the first physiological evidence of a role of presynaptic 5-HT2A receptors located at thalamocortical synapses in the control of thalamofrontal connectivity and the associated cognitive functions.
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Barre
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Berthoux
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Valjent
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Bockaert
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marin
authors.affiliation: Département de Neurosciences, Centre National de la Recherche Scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34094 Montpellier, France; Département de Neurosciences, Institut National de la Santé et de la Recherche Médicale, U1191, F-34094 Montpellier, France; Université de Montpellier, F-34094 Montpellier, France carine.becamel@igf.cnrs.fr.
authors.forename: Carine
authors.initials: C
authors.lastname: Bécamel
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D055724:Electrophysiological Phenomena; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D013788:Thalamus / Q000378:metabolism / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C; D010738:Type C Phospholipases
keywords: 5-HT2A receptors; presynaptic NMDA receptors; serotonin; temporal-dependent plasticity; thalamocortical synapse