Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning
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 r...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2016-03, Vol.113 (10), p.E1382-E1391 |
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| creator | Barre, Alexander Berthoux, Coralie De Bundel, Dimitri Valjent, Emmanuel Bockaert, Joël Marin, Philippe Bécamel, Carine |
| description | 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. |
| doi_str_mv | 10.1073/pnas.1525586113 |
| format | Article |
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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. 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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. 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| subjects | Animal cognition Animals Association Learning - physiology Biological Sciences Blotting, Western Brain Cerebral Cortex - metabolism Cerebral Cortex - physiology Electrophysiological Phenomena Life Sciences Mice, Inbred C57BL Mice, Knockout Microscopy, Fluorescence Neurology Neuronal Plasticity - genetics Neuronal Plasticity - physiology Neuropsychology PNAS Plus Prefrontal Cortex - metabolism Prefrontal Cortex - physiology Protein Kinase C - metabolism Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2A - genetics Receptor, Serotonin, 5-HT2A - metabolism Receptor, Serotonin, 5-HT2A - physiology Receptors, N-Methyl-D-Aspartate - metabolism Receptors, N-Methyl-D-Aspartate - physiology Rodents Schizophrenia Serotonin Synapses - metabolism Synapses - physiology Synaptic Transmission - genetics Synaptic Transmission - physiology Thalamus - metabolism Thalamus - physiology Type C Phospholipases - metabolism |
| title | Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning |
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