Skip to main content
SpringerLink
Log in

Serotonin 1A receptor (5-HT1A) of the sea lamprey: cDNA cloning and expression in the central nervous system

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Serotonergic cells are among the earliest neurons to be born in the developing central nervous system and serotonin is known to regulate the development of the nervous system. One of the major targets of the activity of serotonergic cells is the serotonin 1A receptor (5-HT1A), an ancestral archetypical serotonin receptor. In this study, we cloned and characterized the 3D structure of the sea lamprey 5-HT1A, and studied the expression of its transcript in the central nervous system by means of in situ hybridization. In phylogenetic analyses, the sea lamprey 5-HT1A sequence clustered together with 5-HT1A sequences of vertebrates and emerged as an outgroup to all gnathostome sequences. In situ hybridization analysis during prolarval, larval and adult stages showed a widespread expression of the lamprey 5-ht1a transcript. In P1 prolarvae 5-ht1a mRNA expression was observed in diencephalic nuclei, the rhombencephalon and rostral spinal cord. At P2 prolarval stage the 5-ht1a expression extended to other brain areas including telencephalic regions. 5-ht1a expression in larvae was observed throughout almost all the main brain regions with the strongest expression in the olfactory bulbs, lateral pallium, striatum, preoptic region, habenula, prethalamus, thalamus, pretectum, hypothalamus, rhombencephalic reticular area, dorsal column nucleus and rostral spinal cord. In adults, the 5-ht1a transcript was also observed in cells of the subcommissural organ. Comparison of the expression of 5-ht1a between the sea lamprey and other vertebrates reveals a conserved pattern in most of the brain regions, likely reflecting the ancestral vertebrate condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

5-HT:

Serotonin (5-hydroxytryptamine)

5-HTR:

Serotonin receptor

5-ht1a:

Serotonin 1A receptor gene

5-HT1A:

Serotonin 1A receptor protein

ir:

Immunoreactive

P0–P23:

0–23 days post-hatching prolarvae

CSF-c:

Cerebrospinal fluid-contacting

References

  • Abalo XM, Villar-Cheda B, Meléndez-Ferro M, Pérez-Costas E, Anadón R, Rodicio MC (2007) Development of the serotonergic system in the central nervous system of the sea lamprey. J Chem Neuroanat 34:29–46

    Article  PubMed  CAS  Google Scholar 

  • Acklin SE, Nicholls JG (1990) Intrinsic and extrinsic factors influencing properties and growth patterns of identified leech neurons in culture. J Neurosci 10:1082–1090

    PubMed  CAS  Google Scholar 

  • Albert PR, Zhou QY, Van Tol HH, Bunzow JR, Civelli O (1990) Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. J Biol Chem 265:5825–5832

    PubMed  CAS  Google Scholar 

  • Alewijnse AE, Timmerman H, Jacobs EH, Smit MJ, Roovers E, Cotecchia S, Leurs R (2000) The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H(2) receptor. Mol Pharmacol 57:890–898

    PubMed  CAS  Google Scholar 

  • Antri M, Cyr A, Auclair F, Dubuc R (2006) Ontogeny of 5-HT neurons in the brainstem of the lamprey, Petromyzon marinus. J Comp Neurol 495:788–800

    Article  PubMed  Google Scholar 

  • Antri M, Auclair F, Albrecht J, Djeudjang N, Dubuc R (2008) Serorotoninergic modulation of sensory transmission to brainstem reticulospinal cells. Eur J Neurosci 28:655–667

    Article  PubMed  Google Scholar 

  • Arora KK, Sakai A, Catt KJ (1995) Effects of second intracellular loop mutations on signal transduction and internalization of the gonadotropin-releasing hormone receptor. J Biol Chem 270:22820–22826

    Article  PubMed  CAS  Google Scholar 

  • Azmitia EC, Gannon PJ, Kheck NM, Whitaker-Azmitia PM (1996) Cellular localization of the 5-HT1A receptor in primate brain neurons and glial cells. Neuropsychopharmacology 14:35–46

    Article  PubMed  CAS  Google Scholar 

  • Barreiro-Iglesias A, Villar-Cheda B, Abalo XM, Anadón R, Rodicio MC (2008) The early scaffold of axon tracts in the brain of a primitive vertebrate, the sea lamprey. Brain Res Bull 75:42–52

    Article  PubMed  CAS  Google Scholar 

  • Barreiro-Iglesias A, Villar-Cerviño V, Anadón R, Rodicio MC (2009) A monoclonal antibody as a tool to study the subcommissural organ and Reissner’s fibre of the sea lamprey: an immunofluorescence study before and after a spinal cord transection. Neurosci Lett 464:34–38

    Article  PubMed  CAS  Google Scholar 

  • Barreiro-Iglesias A, Laramore C, Shifman MI, Anadón R, Selzer ME, Rodicio MC (2010) The sea lamprey tyrosine hydroxylase: cDNA cloning and in situ hybridization study in the brain. Neuroscience 168:659–669

    Article  PubMed  CAS  Google Scholar 

  • Barreiro-Iglesias A, Laramore C, Shifman MI (2012) The sea lamprey UNC5 receptors: cDNA cloning, phylogenetic analysis and expression in reticulospinal neurons at larval and adult stages of development. J Comp Neurol. doi:10.1002/cne.23143

    Google Scholar 

  • Blackmer T, Larsen EC, Takahashi M, Martin TF, Alford S, Hamm HE (2001) G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry. Science 292:293–297

    Article  PubMed  CAS  Google Scholar 

  • Bonnin A, Peng W, Hewlett W, Levitt P (2006) Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience 141:781–794

    Article  PubMed  CAS  Google Scholar 

  • Bordoli L, Kiefer F, Arnold K, Benkert P, Battey J, Schwede T (2009) Protein structure homology modeling using SWISS-MODEL workspace. Nat Protoc 4:1–13

    Article  PubMed  CAS  Google Scholar 

  • Buchanan JT, Grillner S (1991) 5-Hydroxytryptamine depresses reticulospinal excitatory postsynaptic potentials in motoneurons of the lamprey. Neurosci Lett 122:71–44

    Google Scholar 

  • Burnet PW, Eastwood SL, Lacey K, Harrison PJ (1995) The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain. Brain Res 676:157–168

    Article  PubMed  CAS  Google Scholar 

  • Butt CM, Zhao B, Duncan MJ, Debski EA (2002) Sculpting the visual map: the distribution and function of serotonin-1A and serotonin-1B receptors in the optic tectum of the frog. Brain Res 931:21–31

    Article  PubMed  CAS  Google Scholar 

  • Chalmers DT, Watson SJ (1991) Comparative anatomical distribution of 5-HT1A receptor mRNA and 5-HT1A binding in rat brain—a combined in situ hybridisation/in vitro receptor autoradiographic study. Brain Res 561:51–60

    Article  PubMed  CAS  Google Scholar 

  • Christenson J, Franck J, Grillner S (1989) Increase in endogenous 5-hydroxytryptamine levels modulates the central network underlying locomotion in the lamprey spinal cord. Neurosci Lett 100:188–192

    Article  PubMed  CAS  Google Scholar 

  • Christenson J, Cullheim S, Grillner S, Hökfelt T (1990) 5-Hydroxytryptamine immunoreactive varicosities in the lamprey spinal cord have no synaptic specializations—an ultrastructural study. Brain Res 512:201–209

    Article  PubMed  CAS  Google Scholar 

  • Cohen AH, Abdelnabi M, Guan L, Ottinger MA, Chakrabarti L (2005) Changes in distribution of serotonin induced by spinal injury in larval lampreys: evidence from immunohistochemistry and HPLC. J Neurotrauma 22:172–188

    Article  PubMed  Google Scholar 

  • Cornide-Petronio ME, Ruiz MS, Barreiro-Iglesias A, Rodicio MC (2011) Spontaneous regeneration of the serotonergic descending innervation in the sea lamprey after spinal cord injury. J Neurotrauma 28:2535–2540

    Article  PubMed  Google Scholar 

  • Cornide-Petronio ME, Anadón R, Rodicio MC, Barreiro-Iglesias A (2012) The sea lamprey tryptophan hydroxylase: new insight into the evolution of the serotonergic system of vertebrates. Brain Struct Funct. doi:10.1007/s00429-012-0412-7

    Google Scholar 

  • Couch JA, Chen J, Rieff HI, Uri EM, Condron BG (2004) robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation. Development 131:997–1006

    Article  PubMed  CAS  Google Scholar 

  • Daubert EA, Condron BG (2010) Serotonin: a regulator of neuronal morphology and circuitry. Trends Neurosci 33:424–434

    Article  PubMed  CAS  Google Scholar 

  • de Miguel E, Anadón R (1987) The development of retina and the optic tectum of Petromyzon marinus, L. A light microscopic study. J Hirnforsch 28:445–456

    PubMed  Google Scholar 

  • del Olmo E, López-Giménez JF, Vilaró MT, Mengod G, Palacios JM, Pazos A (1998) Early localization of mRNA coding for 5-HT1A receptors in human brain during development. Brain Res Mol Brain Res 60:123–126

    Article  PubMed  Google Scholar 

  • Del Tredici AL, Schiffer HH, Burstein ES, Lameh J, Mohell N, Hacksell U, Brann MR, Weiner DM (2004) Pharmacology of polymorphic variants of the human 5-HT1A receptor. Biochem Pharmacol 67:479–490

    Article  PubMed  Google Scholar 

  • Di Prisco GV, Dubuc R, Grillner S (1994) 5-HT innervation of reticulospinal neurons and other brainstem structures in lamprey. J Comp Neurol 342:23–34

    Article  PubMed  Google Scholar 

  • Dinopoulos A, Dori I (1995) The development of the serotonergic fiber network of the lateral ventricles of the rat brain: a light and electron microscopic immunocytochemical analysis. Exp Neurol 133:73–84

    Article  PubMed  CAS  Google Scholar 

  • El Manira A, Zhang W, Svensson E, Bussières N (1997) 5-HT inhibits calcium current and synaptic transmission from sensory neurons in lamprey. J Neurosci 17:1786–1794

    PubMed  CAS  Google Scholar 

  • Grillner S, Deliagina T, Ekeberg O, el Manira A, Hill RH, Lansner A, Orlovsky GN, Wallén P (1995) Neural networks that co-ordinate locomotion and body orientation in lamprey. Trends Neurosci 18:270–279

    PubMed  CAS  Google Scholar 

  • Hardisty MW, Potter IC (1971) The general biology of adult lampreys. In: Hardisty MW, Potter IC (eds) The biology of lampreys, vol 1. Academic Press, London, pp 127–206

    Google Scholar 

  • Hill RH, Svensson E, Dewael Y, Grillner S (2003) 5-HT inhibits N-type but not L-type Ca(2 +) channels via 5-HT1A receptors in lamprey spinal neurons. Eur J Neurosci 18:2919–2924

    Article  PubMed  Google Scholar 

  • Hirunagi K, Ishikawa A, Namikawa T, Uryu K (1995) Immunocytochemical identification of serotonergic supraependymal nerve fibers in the third ventricle of the house musk shrew, Suncus murinus. Ann Anat 177:297–304

    Article  PubMed  CAS  Google Scholar 

  • Kindler S, Kreienkamp HJ (2012) Dendritic mRNA targeting and translation. Adv Exp Med Biol 970:285–305

    Article  PubMed  CAS  Google Scholar 

  • Kroeze WK, Roth BL (2006) Molecular biology and genomic organization of G protein-coupled serotonin receptors. In: Roth BL (ed) The receptors: the serotonin receptors: from molecular pharmacology to human therapeutics. Totowa, New Jersey, pp 1–38

    Google Scholar 

  • Lembo PM, Albert PR (1995) Multiple phosphorylation sites are required for pathway-selective uncoupling of the 5-hydroxytryptamine1A receptor by protein kinase C. Mol Pharmacol 48:1024–1029

    PubMed  CAS  Google Scholar 

  • Malmberg A, Strange PG (2000) Site-directed mutations in the third intracellular loop of the serotonin 5-HT(1A) receptor alter G protein coupling from G(i) to G(s) in a ligand-dependent manner. J Neurochem 75:1283–1293

    Article  PubMed  CAS  Google Scholar 

  • Meléndez-Ferro M, Pérez-Costas E, Villar-Cheda B, Abalo XM, Rodríguez-Muñoz R, Rodicio MC, Anadón R (2002) Ontogeny of gamma-aminobutyric acid-immunoreactive neuronal populations in the forebrain and midbrain of the sea lamprey. J Comp Neurol 446:360–376

    Article  PubMed  Google Scholar 

  • Miquel MC, Kia HK, Boni C, Doucet E, Daval G, Matthiessen L, Hamon M, Vergé D (1994) Postnatal development and localization of 5-HT1A receptor mRNA in rat forebrain and cerebellum. Brain Res Dev Brain Res 80:149–157

    Article  PubMed  CAS  Google Scholar 

  • Nguyen T, Chin WC, O’Brien JA, Verdugo P, Berger AJ (2001) Intracellular pathways regulating ciliary beating of rat brain ependymal cells. J Physiol 531(Pt 1):131–140

    Article  PubMed  CAS  Google Scholar 

  • Nichols DE, Nichols CD (2008) Serotonin receptors. Chem Rev 108:1614–1641

    Article  PubMed  CAS  Google Scholar 

  • Norton WH, Folchert A, Bally-Cuif L (2008) Comparative analysis of serotonin receptor (HTR1A/HTR1B families) and transporter (slc6a4a/b) gene expression in the zebrafish brain. J Comp Neurol 511:521–542

    Article  PubMed  CAS  Google Scholar 

  • Osório J, Rétaux S (2008) The lamprey in evolutionary studies. Dev Genes Evol 218:221–235

    Article  PubMed  Google Scholar 

  • Otaki JM, Firestein S (2001) Length analyses of mammalian G-protein-coupled receptors. J Theor Biol 211:77–100

    Article  PubMed  CAS  Google Scholar 

  • Patel TD, Zhou FC (2005) Ontogeny of 5-HT1A receptor expression in the developing hippocampus. Brain Res Dev Brain Res 157:42–57

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Fernández J, Megías M, Pombal MA (2012) Distribution of a Y1 receptor mRNA in the brain of two lamprey species, the sea lamprey (Petromyzon marinus) and the river lamprey (Lampetra fluviatilis). J Comp Neurol. doi:10.1002/cne.23180

    Google Scholar 

  • Peroutka SJ, Howell TA (1994) The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors. Neuropharmacology 33:319–324

    Article  PubMed  CAS  Google Scholar 

  • Piavis GW (1971) Embryology. In: Hardisty MW, Potter IC (eds) The biology of lampreys, vol 1. Academic Press, London, pp 361–400

    Google Scholar 

  • Pombal MA, Rodicio MC, Anadón R (1996) Secondary vestibulo-oculomotor projections in larval sea lamprey: anterior octavomotor nucleus. J Comp Neurol 372:568–580

    Article  PubMed  CAS  Google Scholar 

  • Pompeiano M, Palacios JM, Mengod G (1992) Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding. J Neurosci 12:440–453

    PubMed  CAS  Google Scholar 

  • Popova NK (2006) From genes to aggressive behavior: the role of serotonergic system. BioEssays 28:495–503

    Article  PubMed  CAS  Google Scholar 

  • Prothmann C, Wellard J, Berger J, Hamprecht B, Verleysdonk (2001) Primary cultures as a model for studying ependymal functions: glycogen metabolism in ependymal cells. Brain Res 920:74–83

  • Richter HG, Tomé MM, Yulis CR, Vío KJ, Jiménez AJ, Pérez-Fígares JM, Rodríguez EM (2004) Transcription of SCO-spondin in the subcommissural organ: evidence for down-regulation mediated by serotonin. Brain Res Mol Brain Res 129:151–162

    Article  PubMed  CAS  Google Scholar 

  • Rubenstein JL (1998) Development of serotonergic neurons and their projections. Biol Psychiatry 44:145–150

    Article  PubMed  CAS  Google Scholar 

  • Saudou F, Boschert U, Amlaiky N, Plassat JL, Hen R (1992) A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. EMBO J 11:7–17

    PubMed  CAS  Google Scholar 

  • Shifman MI, Jin L-Q, Selzer ME (2007) Regeneration in the lamprey spinal cord. In: Becker CG, Becker T (eds) Model organisms in spinal cord regeneration. Wiley-VCH Verlag, Weinheim, pp 229–262

    Google Scholar 

  • Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9

    Article  PubMed  CAS  Google Scholar 

  • Sprouse JS, Aghajanian GK (1988) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology 27:707–715

    Article  PubMed  CAS  Google Scholar 

  • Stam NJ, Van Huizen F, Van Alebeek C, Brands J, Dijkema R, Tonnaer JA, Olijve W (1992) Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes. Eur J Pharmacol 227:153–162

    Article  PubMed  CAS  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  PubMed  CAS  Google Scholar 

  • Taylor JS, Van de Peer Y, Braasch I, Meyer A (2001) Comparative genomics provides evidence for an ancient genome duplication event in fish. Philos Trans R Soc Lond B Biol Sci 356:1661–1679

    Article  PubMed  CAS  Google Scholar 

  • Thamm M, Balfanz S, Scheiner R, Baumann A, Blenau W (2010) Characterization of the 5-HT1A receptor of the honeybee (Apis mellifera) and involvement of serotonin in phototactic behavior. Cell Mol Life Sci 67:2467–2479

    Article  PubMed  CAS  Google Scholar 

  • van Den Berg L, Kwant L, Hestand MS, van Oost BA, Leegwater PA (2005) Structure and variation of three canine genes involved in serotonin binding and transport: the serotonin receptor 1A gene (htr1A), serotonin receptor 2A gene (htr2A), and serotonin transporter gene (slc6A4). J Hered 96:786–796

    Article  Google Scholar 

  • Vígh B, Manzanoe Silva MJ, Frank CL, Vincze C, Czirok SJ, Szabó A, Lukáts A, Szél A (2004) The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain. Histol Histopathol 19:607–628

    PubMed  Google Scholar 

  • Villar-Cheda B, Pérez-Costas E, Meléndez-Ferro M, Abalo XM, Rodríguez-Muñoz R, Anadón R, Rodicio MC (2006) Cell proliferation in the forebrain and midbrain of the sea lamprey. J Comp Neurol 494:986–1006

    Article  PubMed  Google Scholar 

  • Villareal G, Li Q, Cai D, Glanzman DL (2007) The role of rapid, local, postsynaptic protein synthesis in learning-related synaptic facilitation in Aplysia. Curr Biol 17:2073–2080

    Article  PubMed  CAS  Google Scholar 

  • Wallén P, Buchanan JT, Grillner S, Hill RH, Christenson J, Hökfelt T (1989) Effects of 5-hydroxytryptamine on the after hyperpolarization, spike frequency regulation, and oscillatory membrane properties in lamprey spinal cord neurons. J Neurophysiol 61:759–768

    PubMed  Google Scholar 

  • Weiger WA (1997) Serotonergic modulation of behaviour: a phylogenetic overview. Biol Rev Camb Philos Soc 72:61–95

    Article  PubMed  CAS  Google Scholar 

  • Westkaemper RB, Roth BL (2006) Structure and function reveal insights in the pharmacology of 5-HT receptor subtypes. In: Roth BL (ed) The receptors: The serotonin receptors: from molecular pharmacology to human therapeutics. Totowa, New Jersey, pp 39–58

    Google Scholar 

  • Wikström M, Hill R, Hellgren J, Grillner S (1995) The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A-like receptors. Brain Res 678:191–199

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Xunta de Galicia (INCITE08PXIB200063PR) and the Spanish Ministry of Science and Education (BFU2010-17174).

Author information

Authors and Affiliations

  1. Faculty of Biology, Departamento de Biología Celular y Ecología, Edificio CIBUS, Campus Vida, Universidad de Santiago de Compostela, CP. 15782, Santiago de Compostela, A Coruña, Spain

    María Eugenia Cornide-Petronio, Ramón Anadón, Antón Barreiro-Iglesias & María Celina Rodicio

Authors
  1. María Eugenia Cornide-Petronio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramón Anadón
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antón Barreiro-Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. María Celina Rodicio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María Celina Rodicio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cornide-Petronio, M.E., Anadón, R., Barreiro-Iglesias, A. et al. Serotonin 1A receptor (5-HT1A) of the sea lamprey: cDNA cloning and expression in the central nervous system. Brain Struct Funct 218, 1317–1335 (2013). https://doi.org/10.1007/s00429-012-0461-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-012-0461-y

Keywords

Search

Navigation