The morphological changes in the development of serotonergic neurons of the dorsal raphe nuclei in the medulla oblongata was studied by immunocytochemistry in mice with knockout of 1A and 1B serotonin autoreceptors as well as monoamine oxidase A. Serotonin autoreceptors regulate electric activity of serotonergic neurons as well as the synthesis and release of the neurotransmitter, while monoamine oxidase A catalyzes its degradation. These genetic modifications proved to have no effect on the number of serotonergic neurons in the medulla oblongata but induced morphofunctional changes. Decreased cell size and increased intracellular serotonin level were observed in the case of monoamine oxidase A deficiency, while excessive cell size and decreased intracellular serotonin level were observed in the case of autoreceptor deficiency. The data obtained confirm the hypothesis of autoregulation of serotonergic neurons in development.

Ejaculation requires the coordination of sympathetic, parasympathetic and somatic neural outputs. Timely occurrence of the emission and expulsion of sperm results from an interplay between spinal nuclei innervating the seminal tract and the sexual accessory glands including the prostate on the one hand, and on the other hand perineal striated muscles, particularly the bulbospongiosus muscle. A group of cells essential for ejaculation, located around the central canal and referred to as lumbar spinothalamic neurons have been recently identified. Lumbar spinothalamic neurons are immunoreactive for galanin and neurokinin-1 receptor. In order to investigate the anatomical relationships between lumbar spinothalamic neurons and both the prostate and the bulbospongiosus muscle, pseudorabies virus retrograde tracing technique was used combined with immunohistochemistry. Three to five days after pseudorabies virus injection in the bulbospongiosus muscle or the prostate in male rats, spinal cord sections were processed for double immunofluorescence against pseudorabies virus and galanin or neurokinin-1 receptor. Immunocytochemical experiments against pseudorabies virus and choline acetyltransferase were also performed to discriminate between motoneurons and preganglionic neurons, or interneurons. Spinal sections were examined with confocal laser scanning microscope. Three days after pseudorabies virus injection within the prostate and the bulbospongiosus muscle, sympathetic preganglionic neurons and motoneurons of the dorsomedial nucleus were retrogradely labeled, respectively. Five days after pseudorabies virus injection, transsynaptically labeled choline acetyltransferase-negative neurons were found mainly located in the medial gray surrounding the central canal from L1 to S1. At the L3-L4 level, most of transsynaptically labeled neurons were immunoreactive for galanin and to a lesser extent for neurokinin-1 receptor, strongly suggesting that they could be the lumbar spinothalamic cells. We have thus evidenced connections between these cells and motoneurons of the dorsomedial nucleus and both sympathetic and parasympathetic preganglionic neurons innervating the bulbospongiosus muscle and the prostate, respectively. These anatomical data reinforce the crucial role for lumbar spinothalamic cells in coordinating the spinal control of ejaculation.

Up-regulation of the neuronal serotoninergic phenotype in relation to astrocytic population was studied in primary cultures of rat embryonic rostral raphe. Short treatments (18 hr at day in vitro 4) with brain-derived neurotrophic factor (BDNF) or dibutyryl-cAMP (dBcAMP) increased the number of serotoninergic neurons by similar to 80% and similar to 40%, respectively, and markedly enhanced the branching (by 11-fold and 5-fold, respectively) and total length (by 4-fold and 2.5-fold, respectively) of their neurites. Concomitantly, under BDNF treatment, the astrocyte population was decreased by half and became mostly protoplasmic-like. In contrast, dBcAMP treatment also reduced the astrocytic cell density (by one-third) but induced a stellate morphology. Similar short treatment with the astrocyte-derived S100 beta factor induced no modification of the serotonin (5-HT) neuronal phenotype nor of astrocytes morphology. Both BDNF-and cAMP-induced effects were abolished by simultaneous treatment with the specific tyrosine kinase inhibitor genistein, suggesting a role for the high-affinity BDNF receptor tyrosine kinase (TrkB). These data suggest that BDNF and cAMP, but not S100 beta, rapidly induce both an up-regulation of the 5-HT neuronal phenotype and modifications of the neighboring astrocytes in a TrkB-dependent manner. (c) 2005 Wiley-Liss, Inc.

Several lines of evidence indicate that 5-HT7 receptors are involved in pain control at the level of the spinal cord, although their mechanism of action is poorly understood. To provide a morphological basis for understanding the action of 5-HT on this receptor, we performed an immunocytochemical study of 5-HT7 receptor distribution at the lumbar level. 5-HT7 immunolabelling is localized mainly in the two superficial laminae of the dorsal horn and in small and medium-sized dorsal root ganglion cells, which is consistent with a predominant role in nociception. In addition, moderate labelling is found in the lumbar dorsolateral nucleus (Onuf's nucleus), suggesting involvement in the control of pelvic floor muscles. Electron microscopic examination of the dorsal horn revealed three main localizations: 1) a postsynaptic localization on peptidergic cell bodies in laminae I-III and in numerous dendrites; 2) a presynaptic localization on unmyelinated and thin myelinated peptidergic fibers (two types of axon terminals are observed, large ones, presumably of primary afferent origin, and smaller ones partially from intrinsic cells; this presynaptic labelling represents 60% and 22% of total labelling in laminae I and II, respectively); and 3) 16.9% of labelling in lamina I and 19.8% in lamina II are observed in astrocytes. Labeled astrocytes are either intermingled with neuronal elements or make astrocytic "feet" on blood vessels. In dendrites, the labelling is localized on synaptic differentiations, suggesting that 5-HT may act synaptically on the 5-HT7 receptor. This localization is compared with other 5-HT receptor localizations, and their physiological consequences are discussed.

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 24,2005, 8:00 am - 12:00 pm1 Apr 20051067: Triple Immunofluorescent Study of the Spinal Ejaculation Generator Using Retrograde Tracing Technique with 2 Strains of Recombinant Pseudorabies Virus in the Rat with Confocal Microscopy Chen Xu, E. Yaici, M. Conrath, D. Verge, Gérard Benoît, Stéphane Droupy, and François Giuliano Chen XuChen Xu More articles by this author , E. YaiciE. Yaici More articles by this author , M. ConrathM. Conrath More articles by this author , D. VergeD. Verge More articles by this author , Gérard BenoîtGérard Benoît More articles by this author , Stéphane DroupyStéphane Droupy More articles by this author , and François GiulianoFrançois Giuliano More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)35223-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1067: Triple Immunofluorescent Study of the Spinal Ejaculation Generator Using Retrograde Tracing Technique with 2 Strains of Recombinant Pseudorabies Virus in the Rat with Confocal Microscopy." The Journal of Urology, 173(4S), p. 289 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 289 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Chen Xu More articles by this author E. Yaici More articles by this author M. Conrath More articles by this author D. Verge More articles by this author Gérard Benoît More articles by this author Stéphane Droupy More articles by this author François Giuliano More articles by this author Expand All Advertisement PDF downloadLoading ...

Lumbar spinothalannic neurons in the lamina X of the L3-L4 spinal cord segment have been proposed to constitute the spinal ejaculation generator in male rats. Lumbar spinothalannic cells are immunoreactive for galanin and neurokinin-1 receptors. We previously showed that after injection of pseudorabies virus either in the bulbospongiosus muscle or in the prostate, retrogradely labeled cells in the L3-L4 segment also displayed galanin or neurokinin-1 receptor immunoreactivities, demonstrating a direct link between lumbar spinothalamic cells and two anatomical structures involved in the two phases of ejaculation i.e. the emission and the expulsion phases. In order to provide with a more precise anatomical support for the role of lumbar spinothalannic cells in controlling ejaculation, we injected simultaneously in male adult rats two strains of recombinant pseuclorabies virus, expressing either beta-galactosidase (PRV-BaBlu) or green fluorescent protein (PRV-152) in the prostate and in the bulbospongiosus muscle, respectively. After 5 days, we performed multiple immunofluorescence experiments to detect PRV-BaBlu, PRV-152 and galanin or neurokinin-1 receptors in transverse sections of the L1-S1 segment. Double- and triple-labeled cells were counted using confocal laser scanning microscope. Double-labeled neurons with the two strains of pseudorabies virus were mainly found at the L3-L4 segment lateral to the central canal in lamina X and represented about 60% of the total number of pseuclorabies virus-labeled neurons. All the double pseudorabies virus-labeled neurons also expressed lumbar spinothalamic and most of them neurokinin-1 receptor, identifying them as lumbar spinothalamic neurons. The convergence of retrograde labeling from prostate and bulbospongiosus muscle on the same lumbar spinothalannic cells strongly reinforce their role in the spinal control and coordination of the emission and expulsion of sperm. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

Serotonin 5‐HT 1A and 5‐HT 1B receptors and the 5‐HT transporter are key regulators of the serotoninergic neuronal phenotype. We show here that genetic deletion of any of these elements differentially regulates 5‐HT neuronal number in rostral raphe cultures from E14 mice. Serotonin neuronal number was increased by almost four‐fold and 1.8‐fold in cultures from 5‐HT 1A R−/− and 5‐HT 1B R−/− mice, respectively. In contrast, the lack of serotonin transporter expression was associated with a 50% decrease in 5‐HT neuronal number. In raphe cultures from the rat, BDNF and cAMP have been shown to up‐regulate the neuronal serotoninergic phenotype through TrkB‐dependent mechanisms [Rumajogee et al . (2002) J. Neurochem. , 83, 1525–1528]. Similar tyrosine kinase‐dependent up‐regulating effects, in the absence of serotoninergic key‐elements are reported here, on both 5‐HT neuronal number and neurites length. However, the extents of BDNF‐triggered and cAMP‐triggered effects on serotoninergic neuritic length were approximately 1.5‐fold higher in 5‐HT 1A R−/− mutants. These findings show that the up‐regulatory mechanisms triggered by BDNF on serotoninergic neuronal number and neurite extension are different and that the latter are partially linked to 5‐HT, probably through 5‐HT 1A autoreceptors. Together, these data suggest that serotonin autoreceptors, mainly 5‐HT 1A but also 5‐HT 1B , may be responsible for a tonic auto‐inhibitory effect of 5‐HT itself on the serotoninergic neuronal phenotype during embryonic development, particularly marked in the absence of the 5‐HT transporter.

Serotonin (5-HT) plays a major role at the spinal level by modulating most spinal functions through several receptor subtypes including the 5-HT2A receptor. To gain further insight into the cellular role of this receptor, we performed an immunocytochemical study of 5-HT2A receptors in the rat spinal cord, at light and electron microscope levels. The results showed that 5-HT2A receptors were widely distributed in the spinal cord at all segmental levels. Immunolabeling was particularly dense in lamina IX and in the dorsal horn lamina IIi. Immunoreactive cell bodies were numerous in lamina IX, where many but not all motoneurons were labeled, as shown by double labeling with choline acetyltransferase antibodies. Stained cell bodies were also observed in the gray matter. The study at the ultrastructural level focused on the lumbar dorsal horn (laminae I-II) and ventral horn (lamina IX). At both levels, 5-HT2A immunoreactivity was mainly postsynaptic on dendrites and cell bodies. However, a little presynaptic labeling was also observed in axon and axon terminals, some of them containing large granular vesicles attesting to their peptidergic nature. The main result of our study was the "nonsynaptic" plasma membrane localization of 5-HT2A receptors covering a large surface of cell bodies and dendrites, suggesting a paracrine form of action of serotonin. These observations are consistent with a double role (pre- and postsynaptic) for serotonin on these receptors on various cellular targets.

Biology of the CellVolume 96, Issue 5 p. 395-397 Free Access International symposium on G Protein-Coupled Receptors J Cohen-Tannoudji, Corresponding Author J Cohen-Tannoudji Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, France Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Case 256, 4 Place Jussieu, 75252 Paris CEDEX 05, Tel. 01 44 27 26 55 ; Fax. 01 44 27 26 50. E-mail addressjoelle.cohen-tannoudji@snv.jussieu.frSearch for more papers by this authorR Counis, R Counis Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Hervé, D Hervé Transduction du Signal et Plasticité dans le Système Nerveux INSERM U 536, Institut du Fer à Moulin, Université P & M Curie, Paris, FranceSearch for more papers by this authorD.L Shi, D.L Shi Biologie du Développement, CNRS UMR 7622, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Vergé, D Vergé Neurobiologie des Signaux Intercellulaires, CNRS UMR 7101, Université P & M Curie, Paris, FranceSearch for more papers by this author J Cohen-Tannoudji, Corresponding Author J Cohen-Tannoudji Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, France Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Case 256, 4 Place Jussieu, 75252 Paris CEDEX 05, Tel. 01 44 27 26 55 ; Fax. 01 44 27 26 50. E-mail addressjoelle.cohen-tannoudji@snv.jussieu.frSearch for more papers by this authorR Counis, R Counis Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Hervé, D Hervé Transduction du Signal et Plasticité dans le Système Nerveux INSERM U 536, Institut du Fer à Moulin, Université P & M Curie, Paris, FranceSearch for more papers by this authorD.L Shi, D.L Shi Biologie du Développement, CNRS UMR 7622, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Vergé, D Vergé Neurobiologie des Signaux Intercellulaires, CNRS UMR 7101, Université P & M Curie, Paris, FranceSearch for more papers by this author First published: 16 January 2012 https://doi.org/10.1111/j.1768-322X.2004.tb01431.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume96, Issue5June 2004Pages 395-397 RelatedInformation

Biology of the CellVolume 96, Issue 5 p. 325-326 Free Access G Protein-Coupled Receptors: New insights into signaling and regulation J Cohen-Tannoudji, J Cohen-Tannoudji Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, FranceSearch for more papers by this authorR Counis, R Counis Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Hervé, D Hervé Transduction du Signal et Plasticité dans le Système Nerveux INSERM U 536, Institut du Fer à Moulin, Université P & M Curie, Paris, FranceSearch for more papers by this authorD.L Shi, D.L Shi Biologie du Développement, CNRS UMR 7622, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Vergé, Corresponding Author D Vergé Neurobiologie des Signaux Intercellulaires, CNRS UMR 7101, Université P & M Curie, 7, quai Saint-Bernard, 75252 Paris cedex 05, France Tel. 33(0)1 44 27 26 12 ; Fax. 33(0)1 44 27 25 08. E-mail addressDaniel.Verge@snv.jussieu.frSearch for more papers by this author J Cohen-Tannoudji, J Cohen-Tannoudji Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, FranceSearch for more papers by this authorR Counis, R Counis Physiologie et Physiopathologie, CNRS-UMR 7079, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Hervé, D Hervé Transduction du Signal et Plasticité dans le Système Nerveux INSERM U 536, Institut du Fer à Moulin, Université P & M Curie, Paris, FranceSearch for more papers by this authorD.L Shi, D.L Shi Biologie du Développement, CNRS UMR 7622, Université P & M Curie, Paris, FranceSearch for more papers by this authorD Vergé, Corresponding Author D Vergé Neurobiologie des Signaux Intercellulaires, CNRS UMR 7101, Université P & M Curie, 7, quai Saint-Bernard, 75252 Paris cedex 05, France Tel. 33(0)1 44 27 26 12 ; Fax. 33(0)1 44 27 25 08. E-mail addressDaniel.Verge@snv.jussieu.frSearch for more papers by this author First published: 16 January 2012 https://doi.org/10.1111/j.1768-322X.2004.tb01421.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume96, Issue5June 2004Pages 325-326 RelatedInformation

The 5‐HT5A receptor is a seven‐transmembrane receptor negatively coupled to adenylate cyclase, whose activation opens K+ channels. The 5‐HT5A receptor may thus exert an inhibitory effect on neuronal activity. However, the function of this receptor is still largely unknown, in particular at the spinal level, and this is partly due to lack of specific ligands. Immunocytochemistry using specific anti‐5‐HT5A antibodies reveals a particularly dense labeling in the two superficial layers of the dorsal horn, suggesting that the 5‐HT5A receptor may be involved in the spinal modulation of pain. In addition, a very intense staining in the lumbar dorsolateral nucleus (Onuf nucleus) in both males and females suggests that the 5‐HT5A receptor is also involved in micturition through the control of urethral sphincter muscles. Colchicine pretreatment allows the staining of numerous cell bodies in lamina II. Fewer labeled cell bodies are seen in laminae I and III–VI, in the lateral spinal nucleus, and in lamina X. Electron microscope examination of 5‐HT5A receptor immunoreactivity in spinal cords from untreated animals confirmed the postsynaptic labeling in all regions studied (dorsal horn, dorsolateral nucleus, and lamina X). The morphological heterogeneity of labeled dorsal horn cell bodies suggests that they belong to functionally distinct neurons (projection neurons and interneurons). In the lumbar dorsolateral nucleus, the labeling is preferentially localized on dendrites, suggesting that in this nucleus 5‐HT preferentially acts at the dendritic level. Finally, the dense labeling of postsynaptic specializations suggests that the receptor may be in stock before being addressed to the synaptic differentiation. J. Comp. Neurol. 476:316–329, 2004. © 2004 Wiley‐Liss, Inc.

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 11, 2004, 1:00 - 5:00 pm1 Apr 20041643: Neuroanatomical Study of the Ejaculation Generator in the Spinal Cord in Male Rat E.D. Yaici, M. Conrath, D. Verge, A. Jestin, Gérard Benoit, and François Giuliano E.D. YaiciE.D. Yaici More articles by this author , M. ConrathM. Conrath More articles by this author , D. VergeD. Verge More articles by this author , A. JestinA. Jestin More articles by this author , Gérard BenoitGérard Benoit More articles by this author , and François GiulianoFrançois Giuliano More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)38851-7AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1643: Neuroanatomical Study of the Ejaculation Generator in the Spinal Cord in Male Rat." The Journal of Urology, 171(4S), p. 434 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 434 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information E.D. Yaici More articles by this author M. Conrath More articles by this author D. Verge More articles by this author A. Jestin More articles by this author Gérard Benoit More articles by this author François Giuliano More articles by this author Expand All Advertisement Loading ...

In the male rat, serotoninergic neurons of the ventrolateral medulla send direct projections onto spinal preganglionic neurons that innervate the penis. The role of the paraventricular nucleus of the hypothalamus in the control of penile erection is well recognized. Our aim was to demonstrate anatomical relation between paraventricular neurons and medullary serotoninergic neurons innervating the penis. In adult male rats, stereotaxic iontophoretic injections of Phaseolus vulgaris leuco-agglutinin were performed in the paraventricular nucleus. Neurons in the ventrolateral medulla were retrogradely labelled using transneuronal retrograde transport of pseudorabies virus injected in the corpus cavernosum. Sections of the ventro-lateral medulla were processed for double immunofluorescence to reveal both Phaseolus vulgaris leuco-agglutinin and pseudorabies virus using specific antibodies. Sections were also processed for the simultaneous detection of pseudorabies virus and serotonin. Pseudorabies virus-infected neurons in the ventrolateral medulla were present in the nucleus paragigantocellularis, reticular formation of the medulla, raphe pallidus and raphe magnus. In the nucleus paragigantocellularis, all pseudorabies virus-infected-neurons were immunoreactive for serotonin. Some of them received Phaseolus vulgaris leuco-agglutinin-labelled varicose fibres that ran along the soma of pseudorabies virus-infected neurons. Confocal microscopy suggested the presence of several close appositions between them, which were demonstrated using three-dimensional reconstruction of serial optical sections. Our results show that paraventricular neurons send direct projections in the nucleus paragigantocellularis onto neurons that innervate the penis. They suggest a possible role of the paraventricular nucleus in penile erection through the control of descending serotoninergic raphe-spinal neurons. The neurotransmitter used in this pathway remains to be determined.

Following the cloning and sequencing of the A subunit of the 5‐HT3 receptor, two alternatively spliced isoforms, 5‐HT3‐AS and 5‐HT3‐AL, have been identified. In order to analyse the distribution of the receptor, a polyclonal antibody has been produced against the short form which is the most abundant in the central nervous system [Doucet et al. (2000) Neuroscience 95, 881–892]. As expected from the recognition of functional 5‐HT3 receptors, immunostaining by this anti‐5‐HT3‐R‐AS antibody matched the distribution of the high‐affinity 5‐HT3 binding sites in the rat brain and spinal cord. 5‐HT3‐AS‐like immunoreactivity was detected at low levels in the limbic system, particularly in the amygdala and the hippocampus, and in the frontal, piriform and entorhinal cortices. High levels of immunoreactivity were found in the brainstem, mainly in the nucleus tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve, and in the dorsal horn of the spinal cord. At the ultrastructural level, immunostaining was generally found associated with axons and nerve terminals (70–80%) except in the hippocampus, where labelled dendrites were more abundant (56%). This preferential localization on nerve endings is consistent with the well‐documented physiological role of 5‐HT3 receptors in the control of neurotransmitter release. However, the different distribution in the hippocampus raises the question of whether differential addressing mechanisms exist for preferentially targeting 5‐HT3 receptors to postsynaptic dendritic sites as compared to presynaptic nerve endings, depending on the nature of the neurons bearing these receptors.

The effects of brain-derived neurotrophic factor (BDNF) and cAMP on the neuronal serotoninergic phenotype were studied in primary cultures of E14 rat embryonic rostral raphe. Short treatments (for 18 h) with BDNF or dibutyryl-cAMP induced an almost two-fold increase in the number of serotoninergic neurones and a dramatic extension and ramification of their neurites. These changes were associated with marked increases in the levels of mRNAs encoding the serotonin transporter, the 5-HT1A and 5-HT1B receptors and the BDNF receptor tyrosine kinase B (TrkB). Concomitant blockade of tyrosine kinases by genistein suppressed all the up-regulating effects of BDNF and cAMP on 5-hydroxytryptamine (5-HT) neurones. These findings suggest that an auto-amplifying mechanism underlies the promoting effect of BDNF on the differentiation of serotoninergic neurones through TrkB activation, which is also triggered by cAMP.