Skip to main content

Distribution and morphology of serotonin-immunoreactive axons in the retrohippocampal areas of the New Zealand white rabbit

Anatomy and Embryology volume 210, pages 199–207 (2005)Cite this article

Abstract

This study provides a detailed light microscopic description of the morphology and distribution of serotonin-immunoreactive axons in the paleocortical retrohippocampal areas, viz. the subiculum, presubiculum, parasubiculum and entorhinal area, and the adjoining neocortical perirhinal and retrosplenial cortices of the New Zealand white rabbit. Serotonergic axons could be segregated into three different fiber types named fine fibers, beaded fibers and stem-axons. Fine fibers were evenly distributed thin axons with small fusiform/granular varicosities. Beaded fibers were thin axons with large varicosities, predominantly located in the retrohippocampal supragranular layers, where they often formed pericellular arrays. Stem-axons were thick straight, nonvaricose axons seen in the white matter of psalterium dorsale, alveus and the plexiform layer. The paleocortical retrohippocampal areas had a dense supragranular innervation with numerous tortuous fine and beaded fibers, intermingled in conglomerates with conspicuous varicosities forming pericellular arrays. In contrast, the neocortical area 17 and the lateral part of the perirhinal cortex (area 36) were innervated by evenly distributed fine fibers with a moderate number of small varicosities and few ramifications, whereas, the retrosplenial cortex (areas 29e, 29ab and 29cd), and the medial part of the perirhinal cortex (area 35) displayed an intermediate innervation pattern, probably reflecting the transitional nature of these areas being located between the paleo- and the neocortex. The described dualistic innervation pattern may functionally enable the serotonergic system to exert a strong influence on the supragranular layers of the retrohippocampal areas and thus on the neural input entering these areas from the perirhinal and neighboring polymodal association neocortices, whereas the innervation pattern in the adjoining neocortical areas points towards a more diffuse and general modulation of neural activity herein.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Abbreviations

BF:

Beaded fibers

cc:

Corpus callosum

EC:

Entorhinal cortex

FD:

Fascia dentata

F:

Fimbria

FF:

Fine fibers

HF:

Hippocampal fissure

LEC:

Lateral entorhinal cortex

MEC:

Medial entorhinal cortex

PaS:

Parasubiculum

pd:

Psalterium dorsale

PrS:

Presubiculum

rf:

Rhinal fissure

SA:

Stem axons

ss:

Splenial sulcus

Sub:

Subiculum

17:

Area 17, occipitoparietal cortex

29:

Area 29, retrosplenial cortex

35:

Area 35, medial perirhinal cortex

36:

Area 36, lateral perirhinal cortex

I-VI:

Cortical layers I–VI

References

  • Agnati LF, Zoli M, Strömberg I, Witter MP (1995) Intercellular communication in the brain: wiring versus volume transmission. Neuroscience 69(3):711–726

    Article  PubMed  CAS  Google Scholar 

  • Amaral DG, Witter MP (1995) Hippocampal formation. In: Paxinos G (ed) The rat nervous system. Academic, New York, pp 443–493

    Google Scholar 

  • Bjarkam CR, Sørensen JC, Geneser FA (1997) Distribution and morphology of serotonin-immunoreactive neurons in the brainstem of the New Zealand white rabbit. J Comp Neurol 380:507–519

    Article  PubMed  CAS  Google Scholar 

  • Bjarkam CR, Sørensen JC, Geneser FA (2003) Distribution and morphology of serotonin-immunoreactive axons in the hippocampal region of the New Zealand white rabbit. I. Area dentata and hippocampus. Hippocampus 13:21–37

    Article  PubMed  Google Scholar 

  • Brodmann K (1909) Vergleichende Lokalisationslehre der Grosshirnrinde. Barth, Leipzig

    Google Scholar 

  • Burwell RD, Witter MP, Amaral DG (1995) Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature and comparison with findings from the monkey brain. Hippocampus 5:390–408

    Article  PubMed  CAS  Google Scholar 

  • Consolazione A, Milstein C, Wright B, Cuello AC (1981) Immunocytochemical detection of serotonin with monoclonal antibodies. J Histochem Cytochem 29:1425–1430

    PubMed  CAS  Google Scholar 

  • Cumming P, Kretzschmar M, Brust P, Smith DF (2001) Quantitative radioluminography of serotonin uptake sites in the porcine brain. Synapse 39:351–355

    Article  PubMed  CAS  Google Scholar 

  • Dewar KM, Reader TA, Grondin L, Descarries L (1991) [3 H]Paroxetine binding and serotonin content of rat and rabbit cortical areas, hippocampus, neostriatum, ventral mesencephalic tegmentum, and midbrain raphe nuclei region. Synapse 9:14–26

    Article  PubMed  CAS  Google Scholar 

  • Freund TF (1992) GABAergic septal and serotonergic median raphe afferents preferentially innervate inhibitory interneurons in the hippocampus and dentate gyrus. In: The dentate gyrus and its role in seizures (Epilepsy Res Suppl. 7). Chap 5, pp 79–91

  • Freund TF, Buzsáki G (1996) Interneurons of the hippocampus. Hippocampus 6:347–470

    Article  PubMed  CAS  Google Scholar 

  • Freund TF, Gulyás AI, Acsády L, Görcs T, Tóth K (1990) Serotonergic control of the hippocampus via local inhibitory interneurons. Proc Natl Acad Sci 87:8501–8505

    PubMed  Article  CAS  Google Scholar 

  • Geneser FA (1986) Distribution of acetylcholinesterase in the hippocampal region of the rabbit: I. Entorhinal area, parasubiculum, and presubiculum. J Comp Neurol 254:352–368

    Article  PubMed  CAS  Google Scholar 

  • Geneser FA (1987) Distribution of acetylcholinesterase in the hippocampal region of the rabbit: II. Subiculum and hippocampus. J Comp Neurol 262:90–104

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA, Puerto A, Dawsey WJ, Knapp S, Bullard WP, Mandell AJ (1976) Histologic and enzymatic studies of the mesolimbic and mesostrial serotonergic pathways. Brain Res 106:241–256

    Article  PubMed  CAS  Google Scholar 

  • Gulyás AI, Acsády L, Freund TF (1999) Structural basis of the cholinergic and serotonergic modulation of GABAergic neurons in the hippocampus. Neurochem Int 34:359–372

    Article  PubMed  Google Scholar 

  • Halasy K, Miettinen R, Szabat E, Freund TF (1992) GABAergic interneurons are the major postsynaptic targets of median raphe afferents in the rat dentate gyrus. Eur J Neurosci 4:144–153

    PubMed  Article  Google Scholar 

  • Haring JH, Meyerson L, Hoffman TL (1992) Effects of parachloroamphetamine upon the serotonergic innervation of the rat hippocampus. Brain Res 577:253–260

    Article  PubMed  CAS  Google Scholar 

  • Hornung JP, Celio MR (1992) The selective innervation by serotoninergic axons of calbindin-containing interneurons in the neocortex and hippocampus of the marmoset. J Comp Neurol 320:457–467

    Article  PubMed  CAS  Google Scholar 

  • Hornung JP, Fritschy JM, Törk I (1990) Distribution of two morphologically distinct subsets of serotoninergic axons in the cerebral cortex of the marmoset. J Comp Neurol 297:165–181

    Article  PubMed  CAS  Google Scholar 

  • Insausti R, Herrero MT, Witter MP (1997) Entorhinal cortex of the rat: cytoarchitectonic subdivisions and the origin and distribution of cortical efferents. Hippocampus 7:146–183

    Article  PubMed  CAS  Google Scholar 

  • Jakab RL, Goldman-Rakic PS (2000) Segregation of serotonin 5-HT2A and 5-HT3 receptors in inhibitory circuits of the primate cerebral cortex. J Comp Neurol 417:337–348

    Article  PubMed  CAS  Google Scholar 

  • Kellar KJ, Brown PA, Madrid J, Bernstein M, Vernikos-Danellis J, Mehler WR (1977) Origins of serotonin innervation of forebrain structures. Exp Neurol 56:52–62

    Article  PubMed  CAS  Google Scholar 

  • Kia HK, Miquel MC, Brisorgueil MJ, Daval G, Riad M, El Mestikawy S, Hamon M, Vergé D (1996) Immunocytochemical localization of serotonin1A receptors in the rat central nervous system. J Comp Neurol 365:289–305

    Article  PubMed  CAS  Google Scholar 

  • Kilpatrick GJ, Jones BJ, Tyers MB (1989) Binding of the 5-HT3 ligand, [3H]GR65630, to rat area postrema, vagus nerve and the brains of several species. Eur J Pharmacol 365:157–164

    Article  Google Scholar 

  • Köhler C (1984) The distribution of serotonin binding sites in the hippocampal region of the rat brain. An autoradiographic study. Neuroscience 13/3:667–680

    Article  PubMed  Google Scholar 

  • Köhler C, Chan-Palay V, Haglund L, Steinbusch H (1980) Immunohistochemical localization of serotonin nerve terminals in the lateral entorhinal cortex of the rat: demonstration of two separate patterns of innervation from the midbrain raphe. Anat Embryol 160:121–129

    Article  PubMed  Google Scholar 

  • Köhler C, Chan-Palay V, Steinbusch H (1981) The distribution and orientation of serotonin fibers in the entorhinal and other retrohippocampal areas. Anat Embryol 161:237–264

    Article  PubMed  Google Scholar 

  • Kosofsky BE, Molliver ME (1987) The serotonergic innervation of cerebral cortex: different classes of axon terminals arise from dorsal and median raphe nuclei. Synapse 1:153–168

    Article  PubMed  CAS  Google Scholar 

  • Langlais PJ, Mair MG, Anderson CD, McEntee WJ (1987) Monoamines and metabolites in cortex and subcortical structures: normal regional distribution and the effects of thiamine deficiency in the rat. Brain Res 421:140–149

    Article  PubMed  CAS  Google Scholar 

  • Léger L, Charnay Y, Hof PR, Bouras C, Cespuglio R (2001) Anatomical distribution of serotonin-containing neurons and axons in the central nervous system of the cat. J Comp Neurol 433:157–182

    Article  PubMed  Google Scholar 

  • Lidov HGW, Grzanna R, Molliver ME (1980) The serotonin innervation of the cerebral cortex in the rat—an immunohistochemical analysis. Neuroscience 5:207–227

    Article  PubMed  CAS  Google Scholar 

  • Lopes da Silva FH, Witter MP, Boeijinga PH, Lohman AHM (1990) Anatomic organization and physiology of the limbic cortex. Physiol Rev 70(2):453–511

    PubMed  CAS  Google Scholar 

  • Mamounas LA, Molliver ME (1988) Evidence for dual serotonergic projections to neocortex: axons from the dorsal and median raphe nuclei are differentially vulnerable to the neurotoxin p-chloroamphetamine (PCA). Exp Neurol 102:23–36

    Article  PubMed  CAS  Google Scholar 

  • Miettinen R, Freund TF (1992) Convergence and segregation of septal and median raphe inputs onto different subsets of hippocampal inhibitory interneurons. Brain Res 594:263–272

    Article  PubMed  CAS  Google Scholar 

  • Milstein C, Wright B, Cuello AC (1983) The discrepancy between the cross-reactivity of a monoclonal antibody to serotonin and its immunohistochemical specifity. Mol Immunol 20:113–123

    Article  PubMed  CAS  Google Scholar 

  • Molliver ME (1987) Serotonergic neuronal systems: what their anatomic organization tells us about function. J Clin Psychopharmacol 7/6(Suppl):3S–23S

    Google Scholar 

  • Morales M, Bloom F (1997) The 5HT-3 receptor is present in different subpopulations of GABAergic neurons in the rat telencephalon. J Neurosci 17:3157–3167

    PubMed  CAS  Google Scholar 

  • Morales M, Battenberg E, de Lecea L, Bloom F (1996) The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus. Brain Res 731:199–202

    Article  PubMed  CAS  Google Scholar 

  • Mulligan KA, Törk I (1988) Serotoninergic innervation of the cat cerebral cortex. J Comp Neurol 270:86–110

    Article  PubMed  CAS  Google Scholar 

  • Oleskevich S, Descarries L (1990) Quantified distribution of the serotonin innervation in adult rat hippocampus. Neuroscience 34:19–33

    Article  PubMed  CAS  Google Scholar 

  • Oleskevich S, Descarries L, Watkins KC, Séguéla P, Daszuta A (1991) Ultrastructural features of the serotonin innervation in adult rat hippocampus: an immunocytochemical description in single and serial thin sections. Neuroscience 42(3):777–791

    Article  PubMed  CAS  Google Scholar 

  • Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230

    Article  PubMed  CAS  Google Scholar 

  • Pazos A, Cortés R, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors. Brain Res 346:231–249

    Article  PubMed  CAS  Google Scholar 

  • Riad M, Garcia S, Watkins KC, Jodoin N, Doucet E, Langlois X, El Mestikawy S, Hamon M, Descarries L (2000) Somatodendritic localization of 5-HT1A and preterminal axonal localization of 5-HT1B serotonin receptors in adult rat brain. J Comp Neurol 417:191–194

    Article  Google Scholar 

  • Rose M (1931) Cytoarchitektonischer Atlas der Grosshirnrinde des Kaninchens. J Psychol Neur 43:353–440

    Google Scholar 

  • Rose JE, Woolsey CN (1948) Structure and relations of limbic cortex and anterior thalamic nuclei in rabbit and cat. J Comp Neurol 89:279–347

    Article  Google Scholar 

  • Schmitz D, Gloveli T, Empson RM, Heinemann U (1998) Comparison of the effects of serotonin in the hippocampus and the entorhinal cortex. Mol Neurobiol 17(1–3):59–72

    PubMed  CAS  Google Scholar 

  • Suzuki WA, Amaral DG (1990) Cortical inputs to the CA1 field of the monkey hippocampus originate from the perirhinal and parahippocampal cortex but not from area TE. Neurosci Lett 115:43–48

    Article  PubMed  CAS  Google Scholar 

  • Suzuki WA, Amaral DG (1994) Perirhinal and parahippocampal cortices of the macaque monkey: cortical afferents. J Comp Neurol 350:497–533

    Article  PubMed  CAS  Google Scholar 

  • Swanson LW, Köhler C, Björklund A (1987) The limbic region. I. The septohippocampal system. In: Björklund A, Hökfelt T, Swanson LW (eds) Handbook of chemical neuroanatomy, vol. 5, Integrated systems of the CNS, Part I. Elsevier, Amsterdam, pp 125–227

  • Tecott LH, Maricq AV, Julius D (1993) Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proc Natl Acad Sci 90:1430–1434

    PubMed  Article  CAS  Google Scholar 

  • Törk I, Hornung JP (1990) Raphe nuclei and the serotonergic system. In: Paxinos G (ed) The human nervous system. Academic, San Diego, pp 1001–1022

    Google Scholar 

  • Umbriaco D, Garcia S, Beaulieu C, Descarries L (1995) Relational features of acetylcholine, noradrenaline, serotonin and GABA axon terminals in the stratum radiatum of adult rat hippocampus (CA1). Hippocampus 5:605–620

    Article  PubMed  CAS  Google Scholar 

  • Van Hoesen GW (1982) The parahippocampal gyrus: new observations regarding its cortical connections in the monkey. Trends Neurosci 5:345–350

    Article  Google Scholar 

  • Vizi ES, Kiss JP (1998) Neurochemistry and pharmacology of the major hippocampal transmitter systems: synaptic and nonsynaptic interactions. Hippocampus 8:566–607

    Article  PubMed  CAS  Google Scholar 

  • Vogt BA, Sikes RW, Swadlow HA, Weyand TG (1986) Rabbit cingulate cortex: cyto-architecture, physiological border with visual cortex, and afferent cortical connections of visual, motor, postsubicular, and intracingulate origin. J Comp Neurol 248:74–94

    Article  PubMed  CAS  Google Scholar 

  • Wilson MA, Molliver ME (1991) The organization of serotonergic projections to cerebral cortex in primates: regional distribution of axon terminals. Neuroscience 44:537–553

    Article  PubMed  CAS  Google Scholar 

  • Wilson MA, Ricaurte GA, Molliver ME (1989) Distinct morphologic classes of serotonergic axons in primates exhibit differential vulnerability to the psychotropic drug 3,4-methylenedioxymetamphetamine. Neuroscience 28:121–137

    Article  PubMed  CAS  Google Scholar 

  • Witter MP (1993) Organization of the entorhinal-hippocampal system: a review of current anatomical data. Hippocampus 3:33–44

    PubMed  Google Scholar 

  • Witter MP, Groenewegen HJ, Lopes da Silva FH, Lohman AHM (1986) Connections of the parahippocampal cortex in the cat. V. Intrinsic connections; comments on input/output connections with the hippocampus. J Comp Neurol 252:78–94

    Article  PubMed  CAS  Google Scholar 

  • Witter MP, Room P, Groenewegen HJ, Lohman AHM (1989) Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog Neurobiol 33:161–253

    Article  PubMed  CAS  Google Scholar 

  • Woodhams PL, Celio MR, Ulfig N, Witter MP (1993) Morphological and functional correlates of borders in the entorhinal cortex and hippocampus. Hippocampus 3:303–312

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge with gratitude the skillful assistance of Ms. D. Jensen, Ms. K. Wiedemann, Mr. A. Meier, Mr. T. Nielsen and Ms. H. Mikkelsen. Aarhus University Research Foundation, The Foundation for the Advancement of Medical Science and the Novo Nordic Foundation supported the study.

Author information

Affiliations

  1. Department of Neurobiology, Institute of Anatomy, University of Aarhus, 8000, Aarhus C, Denmark

    Carsten R. Bjarkam, Jens Christian Sørensen & Finn A. Geneser

Authors
  1. Carsten R. Bjarkam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jens Christian Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Finn A. Geneser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carsten R. Bjarkam.

Additional information

Grant sponsors: The Aarhus University Research Foundation, the Novo Nordic Foundation and The Foundation for the Advancement of Medical Science.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bjarkam, C.R., Sørensen, J.C. & Geneser, F.A. Distribution and morphology of serotonin-immunoreactive axons in the retrohippocampal areas of the New Zealand white rabbit. Anat Embryol 210, 199–207 (2005). https://doi.org/10.1007/s00429-005-0004-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-005-0004-x

Keywords

  • 5-HT
  • Entorhinal area
  • Paleocortex
  • Perirhinal cortex
  • Retrosplenial cortex