Skip to main content
SpringerLink
Log in

The distribution and orientation of serotonin fibers in the entorhinal and other retrohippocampal areas

An immunohistochemical study with anti-serotonin antibodies in the rat's brain

  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Summary

The serotonin (5-hydroxytryptamine; 5-HT) innervation of the retrohippocampal region (subiculum, pre-and parasubiculum, area 29e, medial and lateral entorhinal area) in the rat brain has been examined with antibodies against 5-HT used in combination with fluorescence histochemistry. Analysis of consecutive sections cut in the coronal, sagittal, and horizontal planes revealed a widespread distribution of 5-HT immunoreactive fibers throughout the retrohippocampal region. This innervation was heterogeneous with regard to the morphological characteristics of the 5-HT fibers, their density and their spatial orientation.

On the basis of morphological criteria, four different types of 5-HT positive processes were distinguished: (a) fine, convoluted fibers with small (∼0.5–0.8 μm), round and evenly spaced varicosities; (b) fine fibers with elongated, irregularly distributed varicosities; (c) thick, possibly myelinated fibers, and (d) a terminal plexus with large (5–10 μm), irregularly spaced varicosities. Analysis of the laminar distribution of the 5-HT fibers showed that whereas all layers contain 5-HT positive fibers, the molecular layer was the most densely innervated. The 5-HT fibers were found to be oriented both parallel and transverse to the longitudinal axis of medial and lateral entorhinal area. This grid-like arrangement was less pronounced in the presubiculum. Although the 5-HT innervation of the retrohippocampal region was found to be dominated by a widespread and apparently diffuse pattern, several areas contained dense clusters of preterminal 5-HT processes: area 29e, dorsal presubiculum (layer II), lateral entorhinal area (layer III and ventral layer II) and the transitional zone of the ventral entorhinal area. The 5-HT fibers were found to enter the retrohippocampal region primarily by three different routes; from the ventral and dorsal aspects and from the piriform and lateral neocortex (via the perirhinal area). Most of the fibers enter the region by the ventral route and these were found to ascend in all layers but predominantly in layer I.

The location of the 5-HT cells giving rise to the innervation of the entorhinal area was studied by combining retrograde transport of fluorescent tracers with immunohistochemistry on the same tissue section. Both ipsi-and contralaterally located cells in the dorsal and median raphe nuclei were found to project to the entorhinal area. Most, but not all, of these retrogradely labeled cell bodies also contain 5-HT immunoreactivity.

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

Similar content being viewed by others

Abbreviations

ab :

angular bundle

ad :

area dentata

cc :

corpus callosum

dcp :

decussation of bracium conjunctivum

dr :

dorsal raphe nucleus (B7)

flm :

medial longitudinal fasciculus

mr :

median raphe nucleus (B8)

occ :

occipital cortex

rtp :

nucleus reticularis tegmentipontis

sub :

subiculum

vtG :

ventral tegmental area of Gudden

III :

third nerve nucleus

28L :

entorhinal area, lateral part

28L′ :

entorhinal area, lateral part (ventral)

28M :

entorhinal area, medial part

28M′ :

entorhinal area, medial part (ventral)

49(a,b) :

parasubiculum

AMYG :

amygdala

Prs :

Presub-presubiculum

TA :

transitional area

TZ :

transitional zone

References

  • Amaral DG, Cowan WM (1980) Subcortical afferents to the hippocampal formation in the monkey. J Comp Neurol 189:573–593

    Google Scholar 

  • Andersen P, Holmquist B, Voorhoeve PE (1966) Entorhinal activation of dentate granule cells. Acta Physiol Scand 66:448–460

    Google Scholar 

  • Andersen P, Bliss TVP, Skrede KK (1971) Lamellar organization of hippocampal excitatory pathway. Exp Brain Res 13:222–238

    Google Scholar 

  • Azmitia EC Jr, Segal M (1978) An autoradiographic analysis of the different ascending projections of the dorsal and median raphe nuclei in the rat. J Comp Neurol 179:641–668

    Google Scholar 

  • Beckstead RM (1978) Afferent connections of the entorhinal area in the rat as demonstrated by retrograde cell labelling with horseradish peroxidase. Brain Res 152:249–264

    Google Scholar 

  • Bentivoglio HG, Kuypers JM, Catsman-Berrevoets CE, Dann O (1979) Fluorescent retrograde neuronal labelling in rat by means of substances binding specifically to adenine-thymine DNA. Neurosci Lett 12:235–240

    Google Scholar 

  • Bjöklund A, Baumgarten HG, Nobin A (1979) Chemical lesioning of central monoamine axons by means of 5,6-dihydroxytryptamine and 5,7-dihydroxytryptamine. In: Costa E, Gressa GL, Sandler M (eds) Adv Biochem Psychopharmacol, 10:13–33. Raven Press, New York

    Google Scholar 

  • Blackstad TW (1956) Commissural connections of the hippocampal region in the rat with special reference to their mode of termination. J Comp Neurol 105:417–538

    Google Scholar 

  • Blackstad TW (1958) On the termination of some afferents to the hippocampus and fascia dentata. An experimental study in the rat. Acta Anat 35:202–214

    Google Scholar 

  • Brownstein MJ, Palkovits M, Saavedra JM, Kizer IS (1975) Tryptophan hydroxylase in the rat brain. Brain Res 17:163–166

    Google Scholar 

  • Chan-Palay V (1975) Fine structure of labelled axons in the cerebellar cortex and nuclei of rodents and primates after intraventricular infusion with tritiated serotonin. Anat Embryol 148:235–265

    Google Scholar 

  • Chan-Palay V (1977a) Cerebellar dentate nucleus: Organization, cytology and transmitters. Springer-Verlag, Heidelberg

    Google Scholar 

  • Chan-Palay V (1977b) Indoleamine neurons and their processes in the normal rat brain and in chronic diet-induced thiamine deficiency demonstrated by uptake of 3H-serotonin. J Comp Neurol 176:467–493

    Google Scholar 

  • Chan-Palay V (1978) Morphological correlates for transmitter synthesis, transport, release, uptake and catabolism: a study of serotonin neurons in the nucleus paragigantocellularis lateralis. Proc of NATO Symp. In: Fonnum F (ed) Amino acid transmitters, 1–29. Plenum Press, New York

    Google Scholar 

  • Conrad LCA, Leonard CM, Pfaff DW, (1974) Connections of the median and dorsal raphe nuclei in the rat. An autoradiographic study. J Comp Neurol 156:179–206

    Google Scholar 

  • Coons AH (1954) Flourescence antibody methods. In: Danielli J-F (ed) General cytochemical methods. Academic Press, New York

    Google Scholar 

  • Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand 64:suppl 232, 1–55

    Google Scholar 

  • Descarries J, Beaudet A, Watkins KC (1975) Serotonin nerve terminals in adult rat neocortex. Brain Res 100:563–588

    Google Scholar 

  • Falck B, Hillarp NA, Thieme G, Torp A (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J Histochem Cytochem 10:348–354

    Google Scholar 

  • Fuxe K (1962) Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol Scand 64:37–85 (Suppl. 247)

    Google Scholar 

  • Haug FMS (1976) Sulphide silver pattern and cytoarchitectonics of parahippocampal areas in the rat. Special references to the subdivisions of area entorhinalis (area 28) and its demarcation from the pyriform cortex. Adv Anat Embryol Cell Biol 52:5–73

    Google Scholar 

  • Hjorth-Simonsen A, Jeune B (1972) Origin and termination of the hippocampal perforant path in the rat. Studied by silver impregnation. J Comp Neurol 144:215–232

    Google Scholar 

  • Jaim-Etcheverry G, Zieher LM (1980) DSP-4, a nove compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523

    Google Scholar 

  • Köhler Ch, 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

    Google Scholar 

  • Köhler Ch, Shipley MT, Srebro B, Harkmark W (1978a) Some retrohippocampal afferents to the entorhinal area of the rat and mouse. Neurosci Lett 10:115–120

    Google Scholar 

  • Köhler Ch, Srebro B, Ögren S-O, Ross SB (1978b) Long-term biochemical and behavioural effects of p-chloroamphetamine in the rat. Ann NY Acad Sci 305:645–663

    Google Scholar 

  • König JFR, Klippel RA (1967) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Krieger, New York

    Google Scholar 

  • Krettek JE, Price JL (1977) Projections from the amygdala complex and adjacent olfactory structures to the entorhinal cortex and subiculum in the rat and cat. J Comp Neurol 172:1723–1751

    Google Scholar 

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

    Google Scholar 

  • Ljungdahl A, Hökfelt T, Goldstein M, Park D (1975) Retrograde peroxidase tracing of neurons combined with transmitter histochemistry. Brain Res 84:313–319

    Google Scholar 

  • Lorens SA, Guldberg HC (1974) Regional 5-hydroxytryptamine following selective midbrain raphe lesions in the rat. Brain Res 78:45–56

    Google Scholar 

  • Moore RY, Halaris AE (1975) Hippocampal innervation by serotonin neurons of the midbrain raphe in the rat. J Comp Neurol 164:171–184

    Google Scholar 

  • O'Keefe J, Nadel L (1979) The hippocampus as a cognitive map. Clarendon Press, Oxford

    Google Scholar 

  • Saavedra JM, Brownstein M, Palkovits M (1974) Serotonin distribution in limbic system of the rat. Brain Res 79:438–441

    Google Scholar 

  • Segal M (1977) Afferents to the entorhinal cortex of the rat studied by the method of retrograde transport of horseradish peroxidase. Exp Neurol 57:750–765

    Google Scholar 

  • Segal M, Landis SC (1974) Afferents to the hippocampus of the rat as studied with the method of retrograde transport of horseradish peroxidase. Brain Res 78:1–15

    Google Scholar 

  • Srebro B, Harkmark W, Köhler Ch (1979) Afferent and efferent projections of the entorhinal cortex in the rat. Neurosci Lett Suppl 143

  • Steinbusch HWM, Verhofstad AAJ, Joosten HWJ (1978) Localization of serotonin in central nervous system by immunohistochemistry: description of a specific and sensitive technique and some applications. Neurosci 3:811–819

    Google Scholar 

  • Steinbusch HWM, van der Kooy D, Verhofstad AAJ, Pellegrino A (1980) Serotonergic and non-serotonergic projections from the nucleus raphe dorsalis to the candatus-putamen complex in the rat studied by combined immuno-fluorescence and fluorescence retrograde axonal labelling technique. Neurosci Lett 19:137–142

    Google Scholar 

  • Steward O (1976) Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat. J Comp Neurol 167:285–314

    Google Scholar 

  • Steward O, Scoville SA (1976) Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat. J Comp Neurol 169:347–370

    Google Scholar 

  • Wyss JM Swanson LW, Cowan WM (1979) A study of subcortical afferents to the hippocampal formation in the rat. Neurosci 4:463–477

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Astra Research Laboratories, Astra Läkemedel AB, Södertälje, Sweden

    Christer Köhler

  2. Department of Neurobiology, Harvard Medical School, Boston, MA, USA

    Victoria Chan-Palay

  3. Department of Anatomy and Embryology, University of Nijmegen, Nijmegen, The Netherlands

    Harry Steinbusch

Authors
  1. Christer Köhler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Victoria Chan-Palay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harry Steinbusch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Köhler, C., Chan-Palay, V. & Steinbusch, H. The distribution and orientation of serotonin fibers in the entorhinal and other retrohippocampal areas. Anat Embryol 161, 237–264 (1981). https://doi.org/10.1007/BF00301824

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00301824

Key words

Search

Navigation