title: Descending 5-hydroxytryptamine raphe inputs repress the expression of serotonergic neurons and slow the maturation of inhibitory systems in mouse embryonic spinal cord.
abstract: Spontaneous synchronous rhythmic activities are a common feature of immature neuronal networks. Although the mechanisms underlying such activities have been studied extensively, whether they might be controlled by modulatory information remains questionable. Here, we investigated the role of descending serotonergic (5-HT) inputs from the medulla to the spinal cord in the maturation of rhythmic activity. We found that in spinal cords maintained, as a whole, in organotypic culture without the medulla, the maturation of spontaneous activity is similar to that found in spinal cords developed in utero. Interestingly, in organotypic cultures without the medulla (i.e., devoid of descending inputs), numerous intraspinal neurons expressed 5-HT, unlike in spinal cords cultivated in the presence of the medulla or matured in utero. We demonstrated that this 5-HT expression was specifically dependent on the absence of 5-HT fibers and was repressed by 5-HT itself via activation of 5-HT(1A) receptors. Finally, to verify whether the expression of 5-HT intraspinal neurons could compensate for the lack of descending 5-HT fibers and play a role in the development of spontaneous activity, we blocked the 5-HT synthesis using p-chlorophenylalanine methyl ester in cultures devoid of the medulla. Surprisingly, we found that this pharmacological treatment did not prevent the development of spontaneous activity but accelerated the maturation of intraspinal inhibition at the studied stages. Together, our data indicate that descending 5-HT raphe inputs (1) repress the expression of spinal serotonergic neurons and (2) slow the maturation of inhibitory systems in mouse spinal cord.
authors.affiliation: Laboratoire de Neurobiologie des Réseaux, Université Bordeaux 1 et Centre National de la Recherche Scientifique Unité Mixte de Recherche 5816, 33405 Talence, France. p.branchereau@lnr.u-bordeaux.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Branchereau
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chapron
authors.forename: Pierre
authors.initials: P
authors.lastname: Meyrand
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D046508:Culture Techniques; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D010134:Fenclonine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D008526:Medulla Oblongata / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010507:Periodicity; D011903:Raphe Nuclei / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; C020261:4-chlorophenylalanine methyl ester; D012701:Serotonin; D010134:Fenclonine