Lack of GSK3β activation and modulation of synaptic plasticity by dopamine in 5-HT1A-receptor KO mice.
Psychiatric disorders are associated with excitation-inhibition (E-I) balance impairment in the prefrontal cortex. However, how the E-I balance is regulated is poorly known. The E-I balance of neuronal networks is linked to the action of numerous neuromodulators such as dopamine and 5-HT. We investigated the role of D2-receptors in tuning the E-I balance in a mouse model of anxiety, the 5-HT1A-receptor KO mice. We focused on synaptic plasticity of excitation and inhibition on layer 5 pyramidal neurons. We show that D2-receptor activation decreases the excitation and favors HFS-induced LTD of excitatory synapses via the activation of GSK3β. This effect is absent in 5-HT1A-receptor KO mice. Our data show that the fine control of excitatory transmission by GSK3β requires recruitment of D2-receptors and depends on the presence of 5-HT1A-receptors. In psychiatric disorders in which the number of 5-HT1A-receptors decreased, therapies should reconsider how serotonin and dopamine receptors interact and control neuronal network activity.
Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197CNRS-Université Paris-Saclay, Bât 446, F-91405, Orsay Cedex, France.
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Meunier
Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197CNRS-Université Paris-Saclay, Bât 446, F-91405, Orsay Cedex, France.
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Cancela
Institut de Neuroscience Paris-Saclay (NeuroPSI), UMR 9197CNRS-Université Paris-Saclay, Bât 446, F-91405, Orsay Cedex, France. Electronic address: philippe.fossier@u-psud.fr.
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D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D019257:Quinpirole / Q000008:administration & dosage; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
C000600618:DRD2 protein, mouse; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D044282:Receptor, Serotonin, 5-HT1A; D019257:Quinpirole; D000071679:Glycogen Synthase Kinase 3 beta
Dopamine; Electrophysiology; Glycogen synthase kinase 3; Prefrontal cortex; Pyramidal neurons; Serotonin