Elsevier

Brain Research

Volume 569, Issue 1, 8 January 1992, Pages 1-13
Brain Research

Research report
Ultrastructural analysis of the serotonin hyperinnervation in adult rat neostriatum following neonatal dopamine denervation with 6-hydroxydopamine

https://doi.org/10.1016/0006-8993(92)90363-EGet rights and content

Abstract

Serotonin (5-HT) immunocytochemistry was used at the electron microscopic level to characterize the ultrastructural features of 5-HT axon terminals (varicosities) hyperinnervating the neostriatum of adult rats, 3 months after a neonatal destruction of the nigrostriatal dopamine system by intraventricular 6-hydroxydopamine. 5-HT-immunostained terminals from the anterior half of the hyperinnervated neostriatum were examined in single thin sections, and compared to their counterparts in vehicle-injected controls with respect to shape, size, organelle content, presence of a synaptic membrane differentiation and composition of the microenvironment. The intrinsic and relational features of the 5-HT-immunostained varicosities were essentially the same in 5-HT-hyperinnervated and control tissue. In particular, the frequency with which these varicosities made synaptic contacts was similarly low in both conditions (6–8% for whole varicosities), as already described in normal adult rat neostriatum. The distributional frequency of elements juxtaposed to the 5-HT-immunostained varicosities was also comparable in control and 5-HT-hyperinnervated tissue. However, in both conditions, there were much fewer dendritic spines in the microenvironment of 5-HT varicosities than around unlabeled terminals randomly selected from the same thin sections. This difference seemed entirely due to the numerous axo-spinous synaptic contacts made by the randomly selected, unlabeled varicosities. Together with recent observations on the 5-HT-hyperinnervation of adult rat hippocampus after grafts of fetal neurons, these data lead to the suggestion that mostly non-junctional neostriatal 5-HT terminals are not committed to a specific intratissular microenvironment. This might in part explain why they grow in excess when reinnervating adult tissue after a lesion or a graft.

References (91)

  • E. Castañeda et al.

    Dopamine depletion in neonatal rats: effects on behavior and striatal dopamine release assessed by intracerebral microdialysis during adulthood

    Brain Research

    (1990)
  • A. Daszuta et al.

    Ultrastructural features of serotonin neurons grafted to adult rat hippocampus. An immunocytochemical analysis of their cell bodies and axon terminals

    Neuroscience

    (1991)
  • A. Daszuta et al.

    Serotonin neurons grafted to adult rat hippocampus. II. 5-HT release as studied by intracerebral microdialysis

    Brain Research

    (1989)
  • A. Daszuta et al.

    Serotonin neurons grafted to the adult rat hippocampus. I. Time course of growth as studied by immunohistochemistry and biochemistry

    Brain Research

    (1988)
  • L. Descarries et al.

    Disappearance of the locus coeruleus in the rat after intraventricular 6-hydroxydopamine

    Brain Research

    (1972)
  • K.M. Dewar et al.

    Elevation of dopamine D2 but not D1 receptors in adult rat neostriatum after neonatal 6-hydroxydopamine denervation

    Brain Research

    (1990)
  • G. Doucet et al.

    Quantification of the dopamine innervation in adult rat neostriatum

    Neuroscience

    (1986)
  • G. Doucet et al.

    Host afferents into intrastriatal transplants of fetal ventral mesencephalon

    Exp. Neurol.

    (1989)
  • T.F. Freund et al.

    Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines

    Neuroscience

    (1984)
  • D. Jackson et al.

    Inhibition of striatal acetylcholine release by serotonin and dopamine after the intracerebral administration of 6-hydroxydopamine to neonatal rats

    Brain Research

    (1988)
  • B.J. Johnson et al.

    D-1 and D-2 receptor contributions to ingestive and locomotor behavior are altered after dopamine depletions in neonatal rats

    Neurosci. Lett.

    (1990)
  • R.J. Konkol et al.

    A biochemical and morphological study of the altered growth pattern of central catecholamine neurons following 6-hydroxydopamine

    Brain Research

    (1978)
  • H.G.W. Lidov et al.

    The structure of cerebral cortex in the rat following prenatal administration of 6-hydroxydopamine

    Dev. Brain Res.

    (1982)
  • H.G.W. Lidov et al.

    An immunohistochemical study of serotonin neuron development in the rat: ascending pathways and terminal fields

    Brain Res. Bull.

    (1982)
  • J. Luthman et al.

    Sprouting of striatal serotonin nerve terminals following selective lesions of nigro-striatal dopamine neurons in neonatal rat

    Brain Res. Bull.

    (1987)
  • F.E. Miller et al.

    Magnitude and duration of hyperactivity following neonatal 6-hydroxydopamine is related to the extent of brain dopamine depletion

    Brain Res.

    (1981)
  • S. Oleskevich et al.

    Ultrastructural features of the serotonin innervation in adult rat hippocampus. An immunocytochemical description in single and serial thin sections

    Neuroscience

    (1991)
  • C. Sachs et al.

    Effects of 6-hydroxydopamine on central noradrenaline neurons during ontogeny

    Brain Research

    (1975)
  • H. Saîdi et al.

    Serotonin reinnervation of the rat organum vasculosum laminae terminalis (OVLT) after 5,7-dihydroxytryptamine deafferentation

    Brain Research

    (1990)
  • R.H. Schmidt et al.

    Regional development of norepinephrine, dopamine-β-hydroxylase and tyrosine hydroxylase in the rat brain subsequent to neonatal treatment with subcutaneous 6-hydroxydopamine

    Brain Research

    (1979)
  • B. Singh et al.

    Altered ontogenesis of central noradrenergic neurons following neonatal treatment with 6-hydroxydopamine

    Brain Research

    (1972)
  • S.P. Sivam et al.

    The adaptation of enkephalin, tachykinin and monoamine neurons of the basal ganglia following neonatal dopaminergic denervation is dependent on the extent of dopamine depletion

    Brain Research

    (1990)
  • J.-J. Soghomonian et al.

    Serotonin innervation in adult rat neostriatum. II. Ultrastructural features: a radio-autographic and immunocytochemical study

    Brain Research

    (1989)
  • J.-J. Soghomonian et al.

    Serotonin innervation in adult rat neostriatum. I. Quantified regional distribution

    Brain Research

    (1987)
  • M.K. Stachowiak et al.

    Apparent sprouting of striatal serotonergic terminals after dopamine-depleting brain lesions in neonatal rats

    Brain Research

    (1984)
  • J.P. Tassin et al.

    Development of cortical and nigro-neostriatal dopaminergic systems after destruction of central noradrenergic neurones in foetal or neonatal rats

    Brain Research

    (1975)
  • A.C. Towle et al.

    Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: an anatomical, biochemical and pharmacological study

    Pharmacol. Biochem. Behav.

    (1989)
  • T. Tsubokawa et al.

    Supranormal levels of serotonin and its metabolite after raphe cell transplantation in serotonin-denervated rat hippocampus

    Brain Res. Bull.

    (1988)
  • S. Ueda et al.

    Reinnervation of serotonin fibers in the denervated rat subcommissural organ by fetal raphe transplants. An immunohistochemical study

    Brain Research

    (1988)
  • P. Voorn et al.

    The pre- and postnatal development of the dopaminergic cell groups in the ventral mesencephalon and the dopaminergic innervation of the striatum of the rat

    Neuroscience

    (1988)
  • I.Q. Whishaw et al.

    Absence of sparing of spatial nagivation, skilled forelimb and tongue use and limb posture in the rat after neonatal dopamine depletion

    Physiol. Behav.

    (1987)
  • L. Wiklund et al.

    Mechanisms of regrowth in the bulbospinal serotonin system following, 5,6-dihydroxytryptamine induced axotomy. II. Fluorescence histochemical observations

    Brain Research

    (1980)
  • A. Björklund et al.

    Growth of transplanted monoaminergic neurons into the adult hippocampus along the perforant path

    Nature

    (1976)
  • O. Bosler et al.

    VIP neurons as prime synaptic targets for serotonin afferents in rat suprachiasmatic nucleus: a combined radioautographic and immunocytochemical study

    J. Neurocytol.

    (1985)
  • G.R. Breese et al.

    Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine

    J. Pharmacol. Exp. Ther.

    (1984)
  • Cited by (139)

    • Enhancing the resolution of behavioral measures: Key observations during a forty year career in behavioral neuroscience

      2023, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      First, we felt compelled, given the striking sub-sensitivity data, to examine the intriguing hypothesis that some other neuronal system had replaced the near-absent DA system in the control of voluntary behavior in these animals. It is noteworthy that soon after the completion of the subtype specific DA antagonist studies discussed above, we reported that in adults lesioned as neonates, but not in adults lesioned as adults, there is a proliferation of serotonin-containing terminals in the striatum (Descarries et al., 1992; Stachowiak et al., 1984). We tested the hypothesis that this sprouting of serotonergic terminals in striatum somehow participated in the plasticity seen in rats lesioned as neonates.

    • Prolongation of absence seizures and changes in serotonergic and dopaminergic neurotransmission by nigrostriatal pathway degeneration in genetic absence epilepsy rats

      2022, Pharmacology Biochemistry and Behavior
      Citation Excerpt :

      Although some studies have shown that striatal serotonin level decreases as a result of 6-OHDA lesions into the MFB or substantia nigra (Brannan et al., 1990; Karstaedt et al., 1994), lack of difference in striatal serotonin level was found in others following intracisternal or intraventricularly administered 6-OHDA (Breese et al., 1984; Erinoff and Snodgrass, 1986). Moreover, an increase in the striatal serotonin level was reported following 6-OHDA injection into the striatum or cortex (Descarries et al., 1992; Dewar et al., 1990). Similarly, the studies investigating in vivo electrophysiological responses to dopamine neurodegeneration induced by 6-OHDA have shown inconstant findings in the firing rates of serotonin neurons of the dorsal raphe nucleus (Guiard et al., 2008; Wang et al., 2009; Zhang et al., 2007).

    • Anatomy of graft-induced dyskinesias: Circuit remodeling in the parkinsonian striatum

      2012, Basal Ganglia
      Citation Excerpt :

      Interestingly, and perhaps of greater significance than the appearance of increased axonal sprouting, is the recent report of a significant increase in 5HT synapses per se in the dyskinetic rat brain [34]. This is of interest because under normal conditions 5HT terminals within the striatum have a very low incidence (†6–∗18%) of actual synapse formation [34⁎,36–38,39†]. Thus, most of the neurotransmitter release in the striatum from 5HT varicosities presumably occurs through autocrine mechanisms.

    View all citing articles on Scopus

    Presented in part at the Third IBRO World Congress of Neuroscience, Montréal, Canada, August 4–9, 1991.

    ∗∗

    Current address: Department of Pharmacology, University of Pennsylvania, John Morgan Building, 36 and Hamilton Walk, Philadelphia, PA 19104, U.S.A.

    View full text