Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning

Alexander Barre, Coralie Berthoux, Dimitri De Bundel, Emmanuel Valjent, Joël Bockaert, Philippe Marin, Carine Bécamel

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E1382-E1391
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number10
DOIs
StatePublished - Mar 8 2016
Externally publishedYes

Keywords

  • 5-HT receptors
  • Presynaptic NMDA
  • Receptors temporal-dependent plasticity
  • Serotonin
  • Thalamocortical synapse

ASJC Scopus subject areas

  • General

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