Skip to main content
Log in

Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Destruction of the dopamine-containing neurons in the rat substantia nigra results in morphological changes in the striatum which have been characterized at both the light and electron microscopic levels. After a unilateral 6-hydroxydopamine injection into the medial forebrain bundle, Golgi-impregnated medium-sized spiny neurons in the neostriatum ipsilateral to the injection had a lower density of spines on their dendrites than those on the contralateral side. A similar decrease in spine density was apparent from 12 days until at least 13.5 months after the lesion. A bilateral loss of spines occurred with increasing age regardless of the presence or absence of the nigrostriatal dopaminergic pathway. At the ultrastructural level, the general pattern of synaptic input to the Golgi-impregnated medium-sized spiny neurons was similar on both sides of the brain. The most obvious class of afferent boutons contacting these spiny neurons formed prominent asymmetrical synaptic specializations with the heads of the spines. The numbers of asymmetric synaptic profiles counted in random electron micrographs from the striata ipsilateral and contralateral to the lesion were not significantly different from each other. A small but significant increase in the length of asymmetric synaptic specialization profiles was, however, detected in the striata lacking a dopamine input.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Akert K, Pfenniger K, Sandri C, Moor H (1972) Freeze etching and cytochemistry of vesicles and membrane complexes in synapses of the central nervous system. In: Pappas GD, Purpura DP (eds) Structure and function of synapses. Raven Press, New York, pp 67–86

    Google Scholar 

  • Arbuthnott GW, Macleod NK, Brown JR, Wright AK, Rutherford A, Ryman A (1987) The action of 6-OH-dopamine on the striatonigral cells in the rat. In: Inactivation of hypersensitive neurons. Liss, New York, pp 223–232

    Google Scholar 

  • Bolam JP, Ingham CA (1990) Combined morphological and histochemical techniques for the study of neuronal microcircuits. In: Van den Pol A, Wouterlood F (eds) Handbook of chemical neuroanatomy, vol. 8. Neuronal microcircuits — combined morphological, immunocytochemical and electrophysiological techniques for the study of synaptic interactions between identified CNS neurons. Elsevier, Amsterdam, pp 125–198

    Google Scholar 

  • Bolam JP, Izzo PN (1988) The postsynaptic targets of substance P-immuoreactive terminals in the rat neostriatum with particular reference to identified spiny striatonigral neurons. Exp Brain Res 70: 361–377

    Google Scholar 

  • Bolam JP, Powell JF, Wu J-Y, Smith AD (1985) Glutamate decarboxylase-immunoreactive structures in the rat neostriatum: a correlated light and electron microscopic study including a combination of Golgi-impregnation with immunocytochemistry. J Comp Neurol 237: 1–20

    Google Scholar 

  • Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between neocortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum. Brain Res 302: 267–275

    Google Scholar 

  • Bryan GK, Riesen AH (1989) Deprived somatosensory-motor experience in stumptailed monkey neocortex: dendritic spine density and dendritic branching of layer IIIB pyramidal cells. J Comp Neurol 286: 208–217

    Google Scholar 

  • Calverley RKS, Jones DG (1990) Contributions of dendritic spines and perforated synapses to synaptic plasticity. Brain Res Rev 15: 215–249

    Google Scholar 

  • Chang HT, Wilson CJ, Kitai ST (1982) A Golgi study of rat neostriatal neurons: light microscopic analysis. J Comp Neurol 208: 107–126

    Google Scholar 

  • Chen S, Hillman DE (1990) Robust synaptic plasticity of striatal cells following partial deafferentation. Brain Res 520: 103–114

    Google Scholar 

  • Chung JW, Hassler R, Wagner A (1977) Degeneration of two of nine types of synapses in the putamen after center median coagulation in the cat. Exp Brain Res 28: 345–361

    Google Scholar 

  • Dube L, Smith AD, Bolam JP (1988) Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-sized spiny neurons in the rat neostriatum. J Comp Neurol 267: 455–471

    Google Scholar 

  • Ferrante RJ, Kowall NW, Richardson EP (1991) Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J Neurosci 11: 3877–3887

    Google Scholar 

  • Fox CA, Andrade AN, Hillman DE, Schwyn RC (1971) The spiny neurons in the primate striatum. A Golgi and electron microscope study. J Hirnforsch 13: 181–201

    Google Scholar 

  • Freund TF, Bolam JP, Bjorklund A, Stenevi U, Dunnett SB, Powell JF, Smith AD (1985) Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study. J Neurosci 5: 603–616

    Google Scholar 

  • Freund TF, Powell JF, Smith AD (1984) Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines. Neuroscience 13: 1189–1215

    Google Scholar 

  • Frotscher M, Rinne U, Hassler R, Wagner A (1981) Termination of cortical afferents on identified neurons in the caudate nucleus of the cat. A combined Golgi-EM degeneration study. Exp Brain Res 41: 329–337

    Google Scholar 

  • Fairén A, Peters A, Saldanha J (1977) A new procedure for examining Golgi impregnated neurons by light and electron microscopy. J Neurocytol 6: 311–337

    Google Scholar 

  • Gerfen CR (1984) The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature 311: 461–464

    CAS  PubMed  Google Scholar 

  • Gerfen CR, Baimbridge KG, Miller JJ (1985) The neostriatal mosaic: compartmental distribution of the calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Nat Acad Sci USA 82: 8780–8784

    Google Scholar 

  • Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250: 1429–1432

    CAS  PubMed  Google Scholar 

  • Gerfen CR, McGinty JF, Scott Young W (1991) Dopamine differentially regulates dynorphin, substance P and enkephalin expression in striatal neurons: In situ hybridization histochemical analysis. J Neurosci 11: 1016–1031

    Google Scholar 

  • Globus A, Scheibel A (1966) Loss of dendrite spines as an index of pre-synaptic terminal patterns. Nature 212: 463–465

    Google Scholar 

  • Globus A, Rosenzweig MR, Bennett EL, Diamond MC (1973) Effects of differential experience on dendritic spine counts in rat cerebral cortex. J Comp Physiol Psychol 82: 175–181

    Google Scholar 

  • Gould E, Allan MD, McEwen BS (1990a) Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone. Brain Res 525: 327–329

    Google Scholar 

  • Gould E, Woolley S, Frankfurt M, McEwen BS (1990b) Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 10: 1286–1291

    Google Scholar 

  • Gray EG (1959) Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscopic study. J Anat (Lond) 93: 420–432

    Google Scholar 

  • Graybiel AM, Ragsdale CW (1979) Fiber connections of the basal ganglia. Prog Brain Res 51: 239–283

    Google Scholar 

  • Gundersen HJG (1977) Notes on the estimation of the numerical density of arbitrary profiles: the edge effect. J Microsc 111: 219–223

    Google Scholar 

  • Hassler R, Chung JW, Rinne U, Wagner A (1978) Selective degeneration of two out of the nine types of synapses in cat caudate nucleus after cortical lesions. Exp Brain Res 31: 67–80

    Google Scholar 

  • Hefti F, Melamed E, Wurtman RJ (1980) Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization. Brain Res 195: 123–137

    Article  CAS  PubMed  Google Scholar 

  • Hogan RN, Baringer JR, Prusiner SB (1987) Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative Golgi analysis. J Neuropathol Exp Neurol 46: 461–473

    Google Scholar 

  • Ingham CA, Hood SH, Arbuthnott GW (1989) Spine density on neostriatal neurons changes with 6-hydroxydopamine lesions and with age. Brain Res 503: 334–338

    Google Scholar 

  • Ingham CA, Hood SH, Arbuthnott GW (1991a) A light and electron microscopical study of enkephalin-immunoreactive structures in the rat neostriatum after removal of the nigrostriatal dopaminergic pathway. Neuroscience 42: 715–730

    Google Scholar 

  • Ingham CA, Hood SH, Arbuthnott GW (1991b) Correlated light and electron microscopy of Golgi-impregnated neostriatal neurons after 6-hydroxydopamine lesions in the rat. In: Bernadi GEA (ed) The basal ganglia III. Plenum Press, New York, pp 21–28

    Google Scholar 

  • Izzo PN, Bolam JP (1988) Cholinergic synaptic input to different parts of spiny striatonigral neurons in the rat. J Comp Neurol 269: 219–234

    Google Scholar 

  • Izzo PN, Graybiel AM, Bolam JP (1987) Characterization of substance P- and [met]enkephalin-immunoreactive neurons in the caudate nucleus of cat and ferret by a single section Golgi procedure. Neuroscience 20: 577–587

    Google Scholar 

  • Kemp JM, Powell TPS (1971a) The structure of the caudate nucleus of the cat: light and electron microscopy. Phil Trans R Soc (Lond) B 262: 383–401

    Google Scholar 

  • Kemp JM, Powell TPS (1971b) The site of termination of afferent fibres in the caudate nucleus. Phil Trans R Soc (Lond) B 262: 413–427

    Google Scholar 

  • Kemp JM, Powell TPS (1971c) The termination of fibres from the cerebral cortex and thalamus upon dendritic spines in the caudate nucleus: a study with the Golgi method. Phil. Trans R Soc (Lond) B 262: 429–439

    Google Scholar 

  • Lescaudron L, Jaffard R, Verna A (1989) Modifications in number and morphology of dendritic spines resulting from chronic ethanol consumption and withdrawal: a Golgi study in the mouse anterior and posterior hippocampus. Exp Neurol 106: 156–163

    Google Scholar 

  • Levine MS, Adinolfi AM, Fisher RS, Hull CD, Buchwald NA, McAllister JP (1986) Quantitative morphology of medium-size caudate spiny neurons in aged cats. Neurobiol Ageing 7: 277–286

    Google Scholar 

  • Levine MS, Adinolfi AM, Fisher RS, Hull CD, Guthrie D, Buchwald NA (1988) Ultrastructural alterations in caudate nucleus in aged cats. Brain Res 440: 267–279

    Google Scholar 

  • Lindefors N, Brene S, Herrera-Marschitz M, Persson H (1989a) Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain. Exp Brain Res 77: 611–620

    Google Scholar 

  • Lindefors N, Brodin E, Tossman U, Segovia J, Ungerstedt U (1989b) Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation. Exp Brain Res 74: 527–534

    Google Scholar 

  • Lindefors N, Brene S, Herrera-Marschitz M, Persson H (1990) Neuropeptide gene expression in brain is differentially regulated by midbrain dopamine neurons. Exp Brain Res 80: 489–500

    Google Scholar 

  • Masuo Y, Pelaprat D, Montagne M-N, Scherman D, Rostene W (1990) Regulation of neurotensin-containing neurons in the rat striatum and substantia nigra. Effects of unilateral nigral lesion with 6-hydroxydopamine on neurotensin content and its binding site density. Brain Res 510: 203–210

    Google Scholar 

  • McNeill TH, Brown SA, Rafols JA, Shoulson I (1988) Atrophy of medium spiny I striatal dendrites in advanced Parkinson's disease. Brain Res 455: 148–152

    Google Scholar 

  • Meshul CK, Casey DE (1989) Regional, reversible ultrastructural changes in rat brain with chronic neuroleptic treatment. Brain Res 489: 338–346

    Google Scholar 

  • Montoya CP, Astell S, Dunnett SB (1990) Effects of nigral and striatal grafts on skilled forelimb use in the rat. In: Dunnett SB, Richards SJ (eds) Neural transplantation from molecular basis to clinical application. Elsevier, Amsterdam New York, pp 459–466

    Google Scholar 

  • Norton S, Culver B (1977) A Golgi analysis of caudate neurons in rats exposed to carbon monoxide. Brain Res 132: 455–465

    Google Scholar 

  • Paxinos G, Watson C (1982) The Rat brain in stereotaxic coordinates. Academic Press, London

    Google Scholar 

  • Rafols JA, Wei Cheng H, McNeill TH (1989) Golgi study of the mouse striatum: age-related dendritic changes in different neuronal populations. J Comp Neurol 279: 212–227

    Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J Cell Biol 17: 208–212

    Article  CAS  PubMed  Google Scholar 

  • Riley JN, Walker DW (1978) Morphological alterations in hippocampus after long-term alcohol consumption in mice. Science 201: 646–648

    Google Scholar 

  • Ruiz-Marcos A, Cartagna Abella P, Garcia Garcia A, Escobar del Rey F, Morreale de Escobar G (1988) Rapid effects of adult-onset hypothyroidism on dendritic spines of pyramidal cells of the rat cerebral cortex. Exp Brain Res 73: 583–588

    Google Scholar 

  • Schultz W (1982) Depletion of dopamine in the striatum as an experimental model of parkinsonism: direct effects and adaptive mechanisms. Prog Neurobiol 18: 121–166

    Google Scholar 

  • Schultz W, Ungerstedt U (1978) Striatal cell sensitivity to apomorphine in dopamine-lesioned rats correlated to behaviour. Neuropharmacology 17: 349–353

    Google Scholar 

  • Schwartz ML, Rothblat LA (1980) Long-lasting behavioral and dendritic spine deficits in the monocularly deprived albino rat. Exp Neurol 68: 136–146

    Google Scholar 

  • Segovia J, Garcia-Munoz M (1987) Changes in the activity of GAD in the basal ganglia of the rat after striatal dopaminergic denervation. Neuropharmacology 26: 1449–1451

    Google Scholar 

  • Sivam SP, Breese GR, Krause JE, Napier TC, Mueller RA, Hong J-S (1987) Neonatal and adult 6-hydroxydopamine-induced lesions differentially alter tachykinin and enkephalin gene expression. J Neurochem 49: 1623–1633

    Google Scholar 

  • Somogyi P, Bolam JP, Smith AD (1981a) Monosynaptic cortical input and local axon collaterals of identified striatonigral neurons. A light and electron microscopic study using the Golgiperoxidase, transport-degeneration procedure. J Comp Neurol 195: 567–584

    CAS  PubMed  Google Scholar 

  • Somogyi P, Freund TF, Halasz N, Kisvarday ZF (1981b) Selectivity of neuronal (3H)GABA accumulation in the visual cortex as revealed by Golgi staining of the labeled neurons. Brain Res 225: 431–436

    Google Scholar 

  • Thal LJ, Sharpless NS, Hirschhorn ID, Horowitz SG, Makman MH (1983) Striatal met-enkephalin concentration increases following nigrostriatal denervation. Biochem Pharmacol 32: 3297–3301

    Google Scholar 

  • Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand [Suppl] 367: 69–93

    Google Scholar 

  • Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res 24: 485–493

    Article  CAS  PubMed  Google Scholar 

  • Uranova NA, Orlovskaya DD, Apel K, Klintsova AJ, Haselhorst U, Schenk H (1991) Morphometric study of synaptic patterns in the rat caudate nucleus and hippocampus under haloperidol treatment. Synapse 7: 253–259

    CAS  PubMed  Google Scholar 

  • Vernier P, Julien J-F, Rataboul P, Fourrier O, Feuerstein C, Mallet J (1988) Similar time course changes in striatal levels of glutamic acid decarboxylase and proenkephalin mRNA following dopaminergic deafferentation in the rat. J Neurochem 51: 1375–1380

    Google Scholar 

  • Vincent SR, Nagy JI, Fibiger HC (1978) Increased striatal glutamate decarboxylase after lesions of the nigrostriatal pathway. Brain Res 143: 168–173

    Google Scholar 

  • Voorn P, Roest G, Groenewegen HJ (1987) Increase of enkephalin and decrease of substance P immunoreactivity in the dorsal and ventral striatum of the rat after midbrain 6-hydroxydopamine lesions. Brain Res 412: 391–396

    Google Scholar 

  • Wishaw IQ, O'Connor WT, Dunnett SB (1986) The contributions of motor cortex, nigrostriatal dopamine and caudate-putamen to skilled forelimb use in the rat. Brain 109: 805–843

    Google Scholar 

  • Xu ZC, Wilson CJ, Emson PC (1992) Morphology of intracellularly stained spiny neurons in rat striatal grafts. Neuroscience 48: 95–110

    Google Scholar 

  • Young WS III, Bonner TI, Brann MR (1986) Mesencephalic dopamine neurons regulate expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci USA 83: 9827–9831

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ingham, C.A., Hood, S.H., van Maldegem, B. et al. Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway. Exp Brain Res 93, 17–27 (1993). https://doi.org/10.1007/BF00227776

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00227776

Key words

Navigation