期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 10, 页码 E1382-E1391出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1525586113
关键词
serotonin; 5-HT2A receptors; thalamocortical synapse; presynaptic NMDA receptors; temporal-dependent plasticity
资金
- Fondation pour la Recherche Medicale
- French National Research Agency [ANR-08-MNPS-0011]
- Soroptimist International-Union Francaise
- CNRS
- INSERM
- University of Montpellier
- Region Languedoc-Roussillon
- University of Montpellier 1
- Gouvernement de la Nouvelle-Caledonie
- Agence Nationale de la Recherche (ANR) [ANR-08-MNPS-0011] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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