Anatomy and Physiology of the Subthalamic Nucleus: A Driving Force of the Basal Ganglia

  • S. T. Kitai
  • H. Kita
Part of the Advances in Behavioral Biology book series (ABBI, volume 32)


The subthalamic (STh) nucleus is located between the zona incerta dorsally and the cerebral peduncle ventrally. The morphological features of STh neurons have been studied extensively at the light microscopic level (Rafols and Fox, 1976; Iwahori, 1978; Yelnik and Percheron, 1979; Hammond and Yelnik, 1983; Kita et al., 1983b; Afsharpour, 1985b) and the electron microscopic level (Rafols and Fox, 1976; Hassler et al., 1982; Chang et al., 1983). Although these studies have proposed different classification schemes for STh neurons, there is an almost complete concensus with regard to the somatic and dendritic morphology of the principal STh neurons in various species. STh neurons are stellate neurons with radiating and sparsely spined dendrites. Ultrastructure studies have demonstrated that the somata of STh neurons contain abundant organelles with nuclei that have deeply invaginated nuclear envelopes and pale nucleoplasm with little heterochromatin. In the neuropil, at least two types of axon terminals were identified. One type of terminal (Gray’s Type I) contained medium-sized round vesicles and formed asymmetrical synapses. The other type of terminal (Gray’s Type II) was large and contained both round and flattened vesicles and formed adherens junctions and symmetrical synapses.


Substantia Nigra Globus Pallidus Subthalamic Nucleus Cerebral Peduncle Zona Incerta 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adinolfi, A.M., 1969, The fine structure of neurons and synapses in the entopeduncular nucleus of the cat, J. Comp. Neurol., 135:225–248.PubMedCrossRefGoogle Scholar
  2. Afsharpour, S., 1985a, Topographical projection of the cerebral cortex to the subthalamic nucleus, J. Comp. Neurol., 236:14–28.PubMedCrossRefGoogle Scholar
  3. Afsharpour, S., 1985b, Light microscopic analysis of Golgi impregnated rat subthalamic neurons, J. Comp. Neurol., 236:1–13.PubMedCrossRefGoogle Scholar
  4. Bak, I.J., Choi, W.B., Hassler, R., Usunoff, K.G., and Wagner, A., 1975, Fine structural synaptic organization of the corpus striatum and substantia nigra in rat and cat, in: “Advances in Neurology, Vol. 9,” D.B. Calne, T.N. Chase, and A. Barbeau, eds., Raven Press, New York, pp.25–41.Google Scholar
  5. Beckstead, R.M., 1983, A reciprocal axonal connection between the subthalamic nucleus and the neostriatum in the cat, Brain Res., 275:137–142.PubMedCrossRefGoogle Scholar
  6. Carpenter, M.B., Fraser, R.A.R. and Shriver, J., 1968, The organization of the pallidosubthalamic fibers in the monkey, Brain Res., 11:522–559.PubMedCrossRefGoogle Scholar
  7. Carpenter, M.B., Batton, R.R. III, Carleton, S.C. and Keller, J.T., 1981a, Interconnections and organization of pallidal and subthalamic nucleus neurons in the monkey, J. Comp. Neurol., 197:579–603.PubMedCrossRefGoogle Scholar
  8. Carpenter, M.B., Carleton, S.C, Keller, J.T. and Conte, P., 1981b, Connections of the subthalamic nucleus in the monkey. Brain Res., 224:1–29.PubMedCrossRefGoogle Scholar
  9. Carter, D.A. and Fibiger, H.C., 1978, The projections of the entopeduncular nucleus and globus pallidus in rat as demonstrated by autoradiography and horseradish peroxidase histochemistry, J. Comp. Neurol., 177:113–124.PubMedCrossRefGoogle Scholar
  10. Chang, H.T., Wilson, C.J, and Kitai, S.T., 1981, Single neostriatal efferent axons in the globus pallidus: A light and electron microscopic study, Science, 213:915–918.PubMedCrossRefGoogle Scholar
  11. Chang, H.T., Kita, H. and Kitai, S.T., 1983, The fine structure of the rat subthalamic nucleus: An electron microscopic study, J. Comp. Neurol., 221:113–123.PubMedCrossRefGoogle Scholar
  12. Chang, H.T., Kita, H. and Kitai, S.T., 1984, The ultrastructural morphology of the subthalamo-nigral axon terminals intracellularly labeled with horseradish peroxidase, Brain Res, 299:182–185.PubMedCrossRefGoogle Scholar
  13. DeLong, M.R. and Alexander, G.E., 1986, Organization of basal ganglia, in: “Diseases of the Nervous System,” A.D. Asbury, G.M. McKhann and W.I. McDonald, eds., W.B. Sanders Co., Philadelphia.Google Scholar
  14. Deniau, J.M., Hammond, C., Chevalier, G. and Feger, J., 1978, Evidence for branched subthalamic nucleus projections to substantia nigra, entopeduncular nucleus and globus pallidus, Neurosci. Letters, 9:117–121.Google Scholar
  15. DiFiglia, M., Pasik, P. and Pasik, T., 1982, A Golgi and ultrastructural study of the monkey globus pallidus, J. Comp. Neurol., 212:53–75.PubMedCrossRefGoogle Scholar
  16. Falls, W.M., Park, M.R. and Kitai, S.T., 1983, An intracellular HRP study of the rat globus pallidus. II. Fine structural characteristics and synaptic connections of medially located large GP neurons, J. Comp. Neurol., 220:229–245.CrossRefGoogle Scholar
  17. Fonnum, F., Grofova, I. and Rinvik, E., 1978, Origin and distribution of glutamate decarboxylase in the nucleus subthalamus of the cat, Brain Res., 153:370–374.PubMedCrossRefGoogle Scholar
  18. Fox, C.A., Andrade, A.N., Lu Qui, I.J. and Rafols, J.A., 1974, The primate globus pallidus: A Golgi and electron microscopic study, J. Hirnforsch., 15:75–93.PubMedGoogle Scholar
  19. Fox, C.A. and Rafols, J.A., 1976, The striatal efferents in the globus pallidus and in the substantia nigra, in: “The Basal Ganglia,” M.D. Yahr, ed., Raven Press, New York, pp. 37–55.Google Scholar
  20. Francois, C., Percheron, G., Yelnik, J. and Heyner, S., 1984, A Golgi analysis of the primate globus pallidus. I. Inconstant processes of large neurons, other neuronal types, and afferent axons, J. Comp. Neurol., 227:182–199.PubMedCrossRefGoogle Scholar
  21. Gerfen, C.R., 1985, The neostriatal mosaic. 1. Compartmental organization of projections from the striatum to the substantia nigra in the rat, J. Comp. Neurol., 236:454–476.PubMedCrossRefGoogle Scholar
  22. Grofova, I., 1969, Experimental demonstration of a topical arrangement of the pallido-subthalamic fibers in the cat, Psychiat. Neurol. Neurochir., 72:53–59.PubMedGoogle Scholar
  23. Grofova, I., 1979, Extrinsic connections of the neostriatum, in: “The Neostriatum,” I. Divac and G.E. Oberg, eds., Pergamon Press, New York, pp. 37–51.Google Scholar
  24. Gulley, R.L., and Smithberg, M., 1971, Synapses in the rat substantia nigra, Tissue & Cell, 3:691–700.CrossRefGoogle Scholar
  25. Hajdu, F., Hassler, R. and Bak, I.J., 1973, Electron microscopic study of the substantia nigra and the strio-nigral projection in the rat, Z. Zeilforsch, 146:207–221.CrossRefGoogle Scholar
  26. Hammond, C., Deniau, J.M., Rizk, A. and Feger, J., 1978, Electrophysiological demonstration of an excitatory subthalamo-nigral pathway in the rat, Brain Res., 151:235–244.PubMedCrossRefGoogle Scholar
  27. Hammond, C., and Yelnik, J., 1983, Intracellular labeling of rat subthalamic neurons with horseradish peroxidase: Computer analysis of dendrites and characterization of axon arborization, Neuroscience, 8:781–790.PubMedCrossRefGoogle Scholar
  28. Hammond, C., Shibazaki, T. and Rouzaire-Dubois, B., 1983, Branched output neurons of the rat subthalamic nucleus: Electrophysiological study of the synaptic effects on identified cells on the two main target nuclei, the entopeduncular nucleus and the substantia nigra, Neuroscience, 9:511–520.PubMedCrossRefGoogle Scholar
  29. Hassler, R., Usunoff, K.G., Romansky, K.V. and Christ, J.F., 1982, Electron microscopy of the subthalamic nucleus in the baboon. I. Synaptic organization of the subthalamic nucleus in the baboon, J. Hirnforsch., 23:597–611.PubMedGoogle Scholar
  30. Iwahori, N., 1978, A Golgi study on the subthalamic nucleus of the cat, J. Comp. Neurol., 182:383–398.PubMedCrossRefGoogle Scholar
  31. Jackson, A., and Grossman, A.R., 1981, Subthalamic nucleus efferent projection to the cerebral cortex, Neuroscience, 6:2367–2377.PubMedCrossRefGoogle Scholar
  32. Kim, R., Nakano, K., Jayaraman, A. and Carpenter, M.B., 1976, Projections of the globus pallidus and adjacent structures: An autoradiographic study in the monkey, J. Comp. Neurol., 169:263–239.PubMedCrossRefGoogle Scholar
  33. Kita, H., Chang, H.T. and Kitai, S.T., 1983a, Pallidal inputs to subthalamus: Intracellular analysis, Brain Res., 264:255–265.PubMedCrossRefGoogle Scholar
  34. Kita, H., Chang, H.T. and Kitai, S.T., 1983b, The morphology of intracellularly labeled rat subthalamic neurons: A light microscopic analysis, J. Comp. Neurol., 215:245–257.PubMedCrossRefGoogle Scholar
  35. Kita, H. and Kitai, S.T., 1987, Efferent projections of the subthalamic nucleus in the rat: Light and electron microscopic analysis with the PHA-L method, J. Comp. Neurol., In press.Google Scholar
  36. Kitai, S.T., and Deniau, J.M., 1981, Cortical inputs to the subthalamus: Intracellular analysis, Brain Res., 214:411–415.PubMedCrossRefGoogle Scholar
  37. Kunzle, H. and Akert, K., 1977, Efferent connections of cortical, area 8 (frontal eye field) in Macaca fascicularis: A reinvestigation using the autoradiographic technique, J. Comp. Neurol., 173:147–164.PubMedCrossRefGoogle Scholar
  38. Kunzle, H., 1978, An autoradiographic analysis of the efferent connections from premotor and adjacent prefrontal regions (areas 6 and 9) in Macaca fascicularis, Brain Behav. Evol., 15:185–234.PubMedCrossRefGoogle Scholar
  39. Levine, M.S., Cherubini, E., Novack, G.D., Hull, C.D. and Buchwald, N.A., 1979, Development of responses of globus pallidus and entopeduncular nucleus neurons to stimulation of the caudate nucleus and precruciate cortex, Exp. Neurol., 66:479–492.PubMedCrossRefGoogle Scholar
  40. McBride, R.L. and Larsen, K.D., 1980, Projections of the feline globus pallidus, Brain Res., 189:3–14.PubMedCrossRefGoogle Scholar
  41. Millhouse, O.E., 1986, Pallidal neurons in the rat, J.Comp Neurol., 254:209–227.PubMedCrossRefGoogle Scholar
  42. Mori, S., 1966, Some observations on the fine structure of the corpus striatum of the rat brain, z.Zellforsch, 70:461–488.PubMedCrossRefGoogle Scholar
  43. Nakamura, S. and Sutin, J., 1972, The pattern of termination of pallidal axons upon cells of the subthalamic nucleus, Exp. Neurol., 35:254–264.PubMedCrossRefGoogle Scholar
  44. Nauta, H.J.W., 1979, Projections of the pallidal complex: An autoradiographic study in the cat, Neuroscience, 4:1853–1873.PubMedCrossRefGoogle Scholar
  45. Nauta, H.J.W. and Cole, M., 1973, Efferent projections of the subthalamic nucleus: An autoradiographic study in monkey and cat, J. Comp. Neurol., 180:1–16.CrossRefGoogle Scholar
  46. Nauta, W.J.H., and Mehler, W.R., 1966, Projections of the lentiform nucleus in the monkey, Brain Res., 1:3–42.PubMedCrossRefGoogle Scholar
  47. Nauta, W.J.H. and Domesick, V.B., 1984, Afferent and efferent relationships of the basal ganglia, in: “Functions of the Basal Ganglia,” D. Evered and M. O’Connor, eds., Pitman Press, Bath, pp. 3–29.Google Scholar
  48. Niimi, K., Ikeda, T., Kawamura, S. and Inoshita, H., 1970, Efferent projections of the head of the caudate nucleus in the cat, Brain Res., 21:327–343.PubMedCrossRefGoogle Scholar
  49. Oertel, W.H. and Mugnaini, E., 1984, Immunocytochemical studies of GABAergic neurons in rat basal ganglia and their relations to other neuronal systems, Neurosci. Letters, 47:233–238.CrossRefGoogle Scholar
  50. Ohye, C., LeGuyader, C. and Feger, J., 1976, Responses of subthalamic and pallidal neurons to striatal stimulation: An extracellular study on awake monkeys, Brain Res., 111:241–252.PubMedCrossRefGoogle Scholar
  51. Park, M.R., Falls, W.W. and Kitai, S.T., 1982, An intracellular HRP study of the rat globus pallidus. I. Responses and light microscopic analysis, J. Comp. Neurol., 211:284–294.PubMedCrossRefGoogle Scholar
  52. Percheron, G., Yelnik, J. and Francois, C., 1984, The primate striato-pallido-nigral system: An integrative system for cortical information, in: “The Basal Ganglia, Structure and Function,” J.S. McKenzie, R.E. Kimm and L.N. Wilcock, eds., Plenum Press, New York, pp. 87–107Google Scholar
  53. Rafols, J.A. and Fox, C.A., 1976, The neurons in the primate subthalamic nucleus: A Golgi and electron microscopic study, J. Comp. Neurol., 168:75–112.PubMedCrossRefGoogle Scholar
  54. Ribak, C.E., 1981, The GABAergic neurons of the extrapyramidal system as revealed by immunocytochemistry, Adv. Biochem. Psychopharmacol., 30:23–37.PubMedGoogle Scholar
  55. Ricardo, J.A., 1980, Efferent connections of the subthalamic region in the rat. 1. The subthalamic nucleus of Luys, Brain Res., 202:257–271.PubMedCrossRefGoogle Scholar
  56. Rinvik, E., and Grofova, I., 1970, Observations on the fine structure of the substantia nigra in the cat, Exp. Brain Res., 11:229–248.PubMedCrossRefGoogle Scholar
  57. Rinvik, E., Grofova, I., Hammond, C. and Deniau, J.M., 1979, A study of the afferent connections to the subthalamic nucleus in the monkey and the cat using the horseradish peroxidase technique, Adv. Neurol., 24:53–69.Google Scholar
  58. Romansky, K.V., Usunoff, K.G., Ivanov, D.P. and Galabov, G.P., 1979, Corticosubthalamic projection in the cat: An electron microscopic study, Brain Res., 163:319–322.PubMedCrossRefGoogle Scholar
  59. Romansky, K.V., Usunoff, K.G., Ivanov, D.P. and Hassler, R., 1980, Pallido-subthalamic projection in the cat, Anat. Embryol., 159:163–180.PubMedCrossRefGoogle Scholar
  60. Rouzaire-Dubois, B., Hammond, C., Hamon, B. and Feger, J., 1980, Pharmacological blockade of the globus pallidus-induced inhibitory reponse of subthalamic cells in the rat, Brain Res., 200:321–329.PubMedCrossRefGoogle Scholar
  61. Rouzaire-Dubois, B., Scarnati, E., Hammond, C., Crossman, A.R. and Shibazaki, T., 1983, Microiontophoretic studies on the nature of neurotransmitter in the subthalamo-entopeduncular pathway of the rat, Brain Res., 271:11–20.PubMedCrossRefGoogle Scholar
  62. Royce, G.J., and Laine, E.J., 1984, Efferent connections of the caudate nucleus including cortical projections of the striatum and other basal ganglia: An autoradiographic and horseradish peroxidase investigation in the cat, J. Comp. Neurol., 226:28–49.PubMedCrossRefGoogle Scholar
  63. Schwyn, R.C., and Fox, C.A., 1974, The primate substantia nigra: A Golgi and electron microscopic study, J. Hirnforsch., 15:95–126.PubMedGoogle Scholar
  64. Szabo, J., 1970, Projection from the body of the caudate nucleus in the rhesus monkey, Exp. Neurol., 27:1–15.PubMedCrossRefGoogle Scholar
  65. Tsubokawa, T. and Sutin, J., 1972, Pallidal and tegmental inhibitions of oscillatory slow waves and unit activity in the subthalamic nucleus, Brain Res., 41:101–118.PubMedCrossRefGoogle Scholar
  66. Usunoff, K.G., Hassler, R., Romansky, K.V., Wagner, A. and Christ, J.F., 1982, Electron microscopy of the subthalamic nucleus in the baboon. II. Experimental demonstration of pallido-subthalamic synapses, J. Hirnforsch., 23:613–625.PubMedGoogle Scholar
  67. Van der Kooy, D. and Hattori, T., 1980, Single subthalamic nucleus neurons project to both the globus pallidus and substantia nigra in rat, J. Comp. Neurol., 192:751–768.CrossRefGoogle Scholar
  68. Van der Kooy, D., Hattori, T., Shannak, K. and Hornykiewicz, O., 1981, The pallido-subthalamic projection in rat: Anatomical and biochemical studies, Brain Res., 204:253–268.PubMedCrossRefGoogle Scholar
  69. VanderMaelen, C.P. and Kitai, S.T., 1980, Intracellular analysis of synaptic potentials in rat neostriatum following stimulation of the cerebral cortex, thalamus, and substantia nigra, Brain Res. Bull., 5:725–733.Google Scholar
  70. Vincent, S.R., Kimura, H. and McGeer, B.G., 1982, GABA transaminase in the basal ganglia: A pharmacohistochemical study, Brain Res., 251:93–104.PubMedCrossRefGoogle Scholar
  71. Von Monakow, W.J.C., Akert, K. and Kunzle, H., 1978, Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey, Exp. Brain Res., 33:395–403.PubMedCrossRefGoogle Scholar
  72. Wilson, C.J. and Phelan, K.D., 1982, Dual topographic representation of neostriatum in the globus pallidus of rats, Brain Res., 243:354–359.PubMedCrossRefGoogle Scholar
  73. Wilson, C.J., Chang, H.T. and Kitai, S.T., 1983, Disfacilitation and long-lasting inhibition of neostriatal neurons in the rat, Exp. Brain Res., 51:227–235.PubMedGoogle Scholar
  74. Wilson, C.J., 1985, Postsynaptic potentials evoked in spiny neostriatal neurons by stimulation of ipsilateral and contralateral neocortex, Brain Res., 367:210–213.Google Scholar
  75. Yelnik, J. and Percheron, G., 1979, Subthalamic neurons in primates: A quantitative and comparative analysis, Neuroscience, 4:1717–1743.PubMedCrossRefGoogle Scholar
  76. Yoshida, M., Rabin, A. and Anderson, M., 1972, Monosynaptic inhibition of pallidal neurons by axon collaterals of caudato-nigral fibers, Exp. Brain Res., 15:333–347.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • S. T. Kitai
    • 1
  • H. Kita
    • 1
  1. 1.Department of Anatomy and NeurobiologyThe University of Tennessee, Memphis College of MedicineMemphisUSA

Personalised recommendations