TY - JOUR
T1 - Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning
AU - Barre, Alexander
AU - Berthoux, Coralie
AU - De Bundel, Dimitri
AU - Valjent, Emmanuel
AU - Bockaert, Joël
AU - Marin, Philippe
AU - Bécamel, Carine
N1 - Funding Information:
We thank Dr. Ingrid Ehrlich (Hertie Institute) and Dr. Fabrice Ango (Institut de Génomique Fonctionnelle) for critically reading the manuscript; and the staff of the animal facility at the Institute of Human Genetics and at the Institute of Functional Genomics for the daily care of animals. This study was supported by grants from the Fondation pour la Recherche Médicale (Contracts Equipe FRM 2005 and 2009), the French National Research Agency (Contract ANR-08-MNPS-0011), The Soroptimist International–Union Française, CNRS, INSERM, and University of Montpellier (to P.M. and C. Bécamel); fellowships from the Région Languedoc-Roussillon, University of Montpellier 1, and the Fondation pour la Recherche Médicale (to A.B.); a fellowship from the Gouvernement de la Nouvelle-Calédonie (to C. Berthoux); and a fellowship from the Fondation pour la Recherche Médicale (to D.D.B.).
PY - 2016/3/8
Y1 - 2016/3/8
N2 - 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.
AB - 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.
KW - 5-HT receptors
KW - Presynaptic NMDA
KW - Receptors temporal-dependent plasticity
KW - Serotonin
KW - Thalamocortical synapse
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U2 - 10.1073/pnas.1525586113
DO - 10.1073/pnas.1525586113
M3 - Article
C2 - 26903620
AN - SCOPUS:84960376021
SN - 0027-8424
VL - 113
SP - E1382-E1391
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -