title: 5-HT(1A) receptors direct the orientation of plasticity in layer 5 pyramidal neurons of the mouse prefrontal cortex.
abstract: Several psychiatric disorders involving the prefrontal cortex (PFC) are associated with a dysfunction of 5-HT(1A) receptors (5-HT(1A)R). These receptors, located on interneurons and pyramidal neurons, may influence neuronal excitability through a regulation of the balance between excitation (E) and inhibition (I). Patch-clamp recordings in mouse cortical slices were performed to determine the modulatory role of 5-HT(1A)R on the excitability and the synaptic plasticity of layer 5 pyramidal neurons (L5PyNs) of the PFC. This was done by a comparison of postsynaptic currents evoked by electrical stimulation in layer 2/3 of 5-HT(1A)R-KO and wild-type (WT) mice. We observed that the E-I balance was significantly changed from 20% E-80% I in WT mice to 23% E-77% I in 5-HT(1A)R-KO mice, demonstrating that 5-HT(1A)Rs contribute to the control of the balance between excitation and inhibition. Furthermore, we show that interfering with 5-HT(1A)R reduced the magnitude of the long term potentiation of excitation (eLTP) (induced by high frequency stimulation). In addition, we show that 5-HT(1A)Rs determine the orientation of the synaptic plasticity towards LTP or LTD or no plasticity through the modulation of NMDAR-mediated currents. Our data point out to a unique role of 5-HT(1A) postsynaptic receptors in PFC to adapt the functional plasticity of L5PyNs towards LTP, LTD or no plasticity. This brings a new way to intervene on neuronal networks of the PFC in anxiety disorders and schizophrenia.
authors.affiliation: Centre de Neuroscience Paris-Sud (CNPS), CNRS UMR 8195, Université Paris Sud, Bâtiment 446, 91405 Orsay, France.
authors.forename: C N J
authors.initials: CN
authors.lastname: Meunier
authors.forename: M
authors.initials: M
authors.lastname: Amar
authors.forename: L
authors.initials: L
authors.lastname: Lanfumey
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: P
authors.initials: P
authors.lastname: Fossier
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
chemical_list: D009419:Nerve Tissue Proteins; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin