Abstract
The notion that the basal ganglia participate in the expression of seizures is long-standing; however, earlier studies focused on striatal-thalamocortical interactions (Jung, 1949; Fariello, 1976; La Grutta et al., 1971; Mutani, 1969). Over the past few years, evidence has accumulated that the substantia nigra (SN) may be an important site to study because it may be involved in seizure control. In 1974, Wada and Sato reported that, during kindled seizures, the electrical activity propagates in the SN bilaterally. Four years later, while studying the anatomical substrates of kindling using the [14C]-2-deoxyglucose technique, Engel et al. (1978) noted that there were striking increases in the metabolic activity of the SN during generalized seizures in adult rats. These investigators postulated that the SN may play an active role in seizures, perhaps mitigating the anticonvulsant effects of the striatum (La Grutta et al., 1971). Subsequently, increases in the metabolic activity of the SN were observed in other animal models of epilepsy (Ben Ari et al., 1981; Lothman and Collins, 1981), in particular when animals experienced generalized seizures. These observations remained unexplored until Iadarola and Gale (1982) reported that pharmacological treatments that increase the GABA transmission of the SN can suppress a variety of experimentally induced seizures in adult rats. At about the same time, we determined that the metabolic changes that occur in the SN during seizures are age-dependent (Ackermann et al., 1982).
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References
Ackermann, R.F., Moshé, S.L., Albala, B.J., and Engel, J., Jr., 1982, Anatomical substrates of amygdala kindling in immature rats demonstrated by 2-deoxyglucose autoradiography, Epilepsia 23: 434–435.
Ackermann, R.F., Chugani, H.T., Handforth, A., Moshé, S.L., Caldecolt-Hazard, S., and Engel, J. Jr., 1986, Autoradiographic studies of cerebral metabolism and blood flow in rat amygdala kindling, in: Kindling 3, (J.A. Wada, ed.), New York: Raven Press, pp. 73–87.
Albala, B.J., Moshé, S.L., and Okada, R., 1984, Kainic acid induced seizures: A developmental study, Dev. Brain Res. 13: 139–148.
Albala, B.J., Moshé, S.L., Cubells, J.F., Sharpless, N.S., and Mackman, M.H., 1986, Unilateral peri-substantia nigra catecholaminergic lesion and amygdala kindling, Brain Res. 370: 388–392.
Amato, G., Sorbera, F., Crescimano, G., and La Grutta, V., 1981, The role of the substantia nigra in the control of amygdaloid paroxysmal activity, Arch. Int. Physiol. Biochem. 89: 91–95.
Beckstead, R.M., 1976, Convergent thalamic and mesencephalic projections to the anterior medial cortex in the rat, J. Comp. Neurol. 166: 403–416.
Ben-Ari, Y., Tremblay, E., Riche, D., Ghilini, G., and Naquet, R., 1981, Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: Metabolic mapping using the de-oxyglucose method with special reference to the pathology of epilepsy, Neurosci. 6: 1361–1391.
Bentivoglio, M., Van Der Kooy, D., and Kuypers, H.G.J.M., 1979, The organization of the efferent projections of the substantia nigra in the rat. A retrograde fluoroscent double labeling studing. Brain Res. 174: 1–17.
Bonhaus, D.W., Walters, J.R., and McNamara, J.O., 1986, Activation of substantia nigra neurons: Role in the propagation of seizures, J. Neurosci. 6: 3024–3030.
Bowery, N.G., Hill, D.R., Hudson, A.L., and Price, G.W., 1988, GABA-B receptors, in: GABA and Benzodiazepine Receptors (R.F. Squires, ed.), Boca Raton, FL: CRC Press, pp. 107–121.
Bowery, N.G., Price, G.W., Hudson, A.L., Hill, D.R., Wilkin, G.P., and Turnbull, M.J., 1984, GABA receptor multiplicity. Visualization of different receptor types in the mammalian CNS, Neuropharmacology 23: 219–231.
Cavalheiro, E.A., Silva, D.F., Turski, W.A., Calderazzo-Filho, L.S., Bartolotto, Z.A., and Turski, L., 1987, The susceptibility of rats to pilocarpine-induced seizures is age dependent, Dev. Brain Res. 37: 43–58.
Chevalier, G., Thierry, T., Shibazaki, T., and Féger, J., 1981, Evidence for a GABAergic inhibitory nigrotectal pathway in the rat, Neurosci. Lett. 21: 67–70.
Deniau, J.M., Hammond, C., and Riszk, A., and Féger, J., 1978, Electrophysiological properties of identified output neurons of the rat substantia nigra (pars compacta and pars reticulata); Evidences for the existence of branched neurons, Exp. Brain Res. 32: 409–422.
Deniau, J.M., Kitai, S.T., Donoghue, J.P., and Grofova, I., 1982, Neuronal interactions in the substantia nigra pars reticulata through axon collaterals of the projection neurons, Exp. Brain Res. 47: 105–113.
De Sarro, G.B., Meldrum, B., and Reaville, C., 1984, Anticonvulsant action of 2-amino-7 phos-phonoheptanoic acid in the substantia nigra, Eur.J. Pharmacol. 106: 175–179.
Dray, A., 1980, The physiology and pharmacology of mammalian basal ganglia. Prog. Neurobiol. 14: 211–335.
Engel, J., Jr., Brown, L.L., and Wolfson, L., 1978, Anatomical correlates of electrical and behavioral events related to amygdaloid kindling, Ann. Neurol. 3: 538–544.
Enna, S.J., 1988, GABA A Receptors in: GABA and Benzodiazepine Receptors. (R.F. Squires, ed.), Boca Raton, FL: CRC Press, pp. 91–106.
Fariello, R., 1976, Forebrain influences on an amygdala acute focus in the cat, Exp. Neurol. 51: 515–528.
Fariello, R., and Hornykiewicz, O., 1979, Substantia nigra and pentylenetetrazol threshold in rats: Correlation with striatal dopamine metabolism, Exp. Neurol. 65: 202–208.
Faull, R., 1985, Thalamus, in: The Rat Nervous System (G. Paxinos, ed.), New York: Academic Press, pp. 129–168.
Franck, J.E., and Schwartzkroin, P.A., 1987, The genetic epilepsy prone rat has altered GABA receptor binding in substantia nigra but not in inferior colliculus, Soc. Neurosci. Abst. 13: 944.
Frye, G.D., McCowan, T.J., and Breese, G.R., 1983, Characterization of susceptibility to audiogenic seizures in ethanol-dependent rats after microinjection of gamma-aminobutyric acid (GABA) agonists into the inferior colliculus, substantia nigra or medial septum, J. Pharmacol. Exp. Ther. 227: 663–670.
Gale, K., 1985, Mechanisms of seizure control mediated by gamma-aminobutyric acid: Role of the substantia nigra, Fed. Am. Soc. Exp. Biol. 44: 2414–2424.
Garant, D.S., and Gale, K., 1983, Lesions of substantia nigra protect against experimentally induced seizures, Brain Res. 273: 156–161.
Garant, D., and Gale, K., 1986, Intranigral muscimol attenuates electrographic signs of seizure activity induced by intravenous bicuculline in rats, Eur. J. Pharmacol. 124: 365–369.
Garant, D., and Gale, K., 1987, Substantia nigra-mediated anticonvulsant actions: Role of nigral output pathways, Exp. Neurol. 97: 143–159.
Garcia-Cairasco, N., and Sabbatini, R.M.E., 1983, Role of the substantia nigra in audiogenic seizures: a neuroethological analysis in the rat, Brazilian J. Med. Biol. Res. 16: 171–183.
Gastaut, H., Gastaut, J.L., Gonzaleze Silva, S.E., and Fernandez-Sanchez, G.E., 1975, Relative frequency of different types of epilepsy. A study employing the classification of the International League Against Epilepsy, Epilepsia 16: 457–461.
Gibbs, F.A., and Gibbs, E.L., 1963, Age factor in epilepsy. TV. Engl. J. Med. 269: 1230–1236.
Gonzalez, L.P., and Hettinger, M.K., 1984, Intranigral muscimol suppresses ethanol withdrawal seizures, Brain Res. 298: 163–166.
Grace, A.A., and Bunney, B.S., 1979, Paradoxical GABA excitation of nigral dopaminergic cells: Indirect mediation through reticulata inhibitory neurons, Eur. J. Pharmacol. 59: 211–218.
Hauser, W.A., and Kurland, L.T., 1975, The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967, Epilepsia 16: 1–66.
Heimer, L., Alheid, G., and Zaborszky, L., 1985, Basal ganglia, in: The Rat Nervous System (G. Paxinos, ed.), New York: Academic Press, pp. 37–85.
Heyer, E.J., Nowak, L.M., and MacDonald, R.L., 1981, Bicuculline: A convulsant with synaptic and nonsynaptic actions, Neurology 31: 1381–1390.
Hill, D.R., and Bowery, N.G., 1981, 3H-Baclofen and 3H-GABA bind to bicuculline insensitive GABAB sites in rat brain, Nature (Lond.) 290: 149–152.
Hosford, D.A., and McNamara, J.O., 1988, Microinjection of muscimol into entopeduncular nucleus suppresses pilocarpine but not maximal electroshock seizures in rats, Brain Res. 462: 205–210.
Howse, D.C., 1983, Cerebral energy metabolism during experimental status epilepticus, in: Advances in Neurology, Status Epilepticus (A. Delgado-Escueta, C.G. Wasterlain, D.M. Treiman, and R.J. Porter, eds.), New York: Raven Press, pp. 34: 209–216.
Huerta, M.F., and Harting, J.K., 1984, The mammalian superior colliculus: studies of its morphology and connections, in: Comparative Neurology of the Optic Tectum (H. Vanegas, ed.), New York: Plenum Press, pp. 687–773.
Iadarola, M.J., and Gale, K., 1982, Substantia nigra: Site of anticonvulsant activity mediated by gamma-aminobutyric, Science 218: 1237–1240.
Johnston, G.A.R., 1986, Multiplicity of GABA receptors, in: Benzodiazepine / GABA Receptors and Chloride Channels (R.W. Olsen, and J.G. Venter, eds.), New York: Alan R. Liss, pp. 55–71.
Jones, E.G., and Leavitt, R.Y., 1974, Retograde axonal transport and the demonstration of nonspecific projections to the cerebral cortex and striatum from thalamic intralaminar nuclei in the rat, cat and monkey, J. Comp. Neurol. 154: 349–378.
Jung, R., 1949, Hirnelektrische Untersuchungen über den Elektrokrampf: Die Erregunsablä ufe in corticalen und subcorticalen Hirnregionen bei Katze und Hund, Arch. Psychiar. Nerve nkr. 183: 206–244.
Karabelas, A.B., and Purpura, D.P., 1980, Evidences for autapses in the substantia nigra, Brain Res. 200: 467–473.
Krettek, J.E., and Price, J.L., 1978, Amygdaloid projections to subcortical structures within the basal forebrain and brainstem of the rat and cat, J. Comp. Neurol. 178: 225–254.
La Grutta, V., Amato, G., and Zagami, M.T., 1971, The importance of the caudate nucleus in the control of convulsive activity in the amygdaloid complex and the temporal cortex of the rat, Electroen-cephalogr. Clin. Neurophysiol. 31: 57–69.
Lazarova, M., Przewlocka, B., Mogilnicka, E., and Stala, L., 1979, The effect of L-Dopa and L-5-hydroxytryptophan on the pentetrazole seizures in rats after lesions of the median raphé nucleus and substantia nigra, Pol. J. Pharmacol. Pharm. 31: 57–69.
LeGal LaSalle, G., Kajima, M., and Feldblum, S., 1983, Abortive amygdaloid kindling seizures following microinjections of gamma-vinyl-GABA in the vicinity of substantia nigra in rats, Neurosci. Lett. 36: 69–74.
Lothman, E.W., and Collins, R.C., 1981, Kainic acid induced limbic seizures: Metabolic, behavioral, electroencephalographic and neuropatho-logical correlates, Brain Res. 218: 99–318.
Loughlin, S.E., and Fallon, J.H., 1984, Substantia nigra and ventral tegmental area projections to cortex; topography and collateralization, Neuroscience 11: 425–435.
Löscher, W., and Schwark, W.S., 1985, Evidence for impaired GABA-ergic activity in the substantia nigra in amygdaloid kindled rats, Brain Res. 339: 146–150.
Löscher, W., and Schwark, W.S., 1987, Further evidence for abnormal GABAergic circuits in amygdala-kindled rats, Brain Res. 420: 385–390.
MacLeod, N.K., James, T.A., Kilpatrick, I.C., and Starr, M.S., 1980, Evidence for a GABAergic ni-grothalamic pathway in the rat. II. Electrophys-ical studies, Exp. Brain Res. 40: 55–61.
McNamara, J.O., Galloway, M.T., Rigsbee, L.L., and Shin, C., 1984, Evidence implicating substantia nigra in regulation of kindled seizure threshold. J. Neurosci. 4: 2410–2417.
Morimoto, K., and Goddard, G.V., 1987, The substantia nigra is an important site for the containment of seizure generalization in the kindling model of epilepsy, Epilepsia 28: 1–10.
Moshé, S.L., 1981, The effects of age on the kindling phenomenon, Dev. Psychobiol. 14: 75–81.
Moshé, S.L., and Albala, B.J., 1983, Maturational changes in postictal refractoriness and seizure susceptibility in developing rats, Ann. Neurol. 13: 552–557.
Moshé, S.L., and Albala, B.J., 1984, Nigral muscimol infusions facilitate the development of seizures in immature rats, Dev. Brain Res. 13: 305–308.
Moshé, S.L., Albala, B.J., Ackermann, R.F., and Engel, J., Jr., 1983, Increased seizure susceptibility of the immature brain, Dev. Brain Res. 7: 81–85.
Moshé, S.L., Okada, R., and Albala, B.J., 1985, Ventromedial thalamic lesions and seizure susceptibility, Brain Res. 337: 368–372.
Moshé, S.L., Ackermann, R.F., Albala, B.J., and Okada, R., 1986, The role of substantia nigra in seizures of developing animals, in: Kindling 3 (J.A. Wada, ed.), New York: Raven Press, pp. 91–106.
Moshé, S.L., Sperber, E.F., Wurpel, J.N.D., and Sharpless, N.S., 1987, Age related changes in striatal dopamine activity following nigral muscimol infusions. Dev. Brain Res. 31: 129–132.
Moshé, S.L., Sperber, E.F., Brown, L.L., Tempel, A., and Wurpel, J.N.D., 1988, Experimental Epilepsy: Developmental aspects, Clev. Clin. J. Med. 56:S92–99.
Mutani, R., 1969, Experimental evidence for the existence of an extrarhincephalic control of the activity of the cobalt rhinencephalic epileptogenic focus. Part I. The role played by the caudate nucleus, Epilepsia 10: 337–350.
Nitsch, C., Schmude, B., and Haug, P., 1983, Alterations in the content of amino acid neurotransmitters before the onset and during the course of methoxypyridoxine-induced seizures in individual rabbit brain regions, J. Neurochem. 40: 1571–1580.
Nevander, G., Ingvar, M., Auer, R., and Siesjø, B.K., 1985, Status epilepticus in well-oxygenated rats causes neuronal necrosis. Ann. Neurol. 18: 281–290.
Okada, Y., Nitsch-Hassler, C., Kim, J.S., Bak, I.J., and Hassler, R., 1971, Role of gamma-aminobutyric (GABA) in the extrapyramidal motor system. 1. Regional distribution of GABA in rabbit, rat, guinea pig, and baboon CNS, Exp. Brain Res. 13: 514–518.
Okada, R., Moshé, S.L., Wong, B.Y., Sperber, E.F., and Zhao, D., 1986, Age related substantia nigra mediated seizure facilitation, Exp. Neurol. 93: 180–187.
Okada, R., Nagishi, N., and Nagaya, H., 1989, The role of the nigrotegmental GABAergic pathway in the propagation of pentylenetetrazol induced seizures, Brain Res. 480: 383–387.
Olsen, R.W., Bann, M., and Miller, T., 1976, Studies on the neuropharmacological activity of bicu-culline and related compounds, Brain Res. 102: 283–299.
Olsen, R.W., Snowhill, E.W., and Wamsley, J.K., 1983, Autoradiographic localization of low affinity GABA receptors with 3H-bicuculline metho-chloride, Eur. J. Pharmacol. 99: 247–248.
Rondouin, G.R., Chicherportiche, M., Lerner-Natoli, M., Ben-Attia, A., Privat, and Baldy-Moulinier, A., 1986, Inhibitory processes in limbic kindling, in: Kindling Vol. 5 (J.A. Wada, ed.), New York: Raven Press, pp. 361–371.
Savage, D.D., Reigel, C.E., and Jobe, P.C., 1986, Angular bundle kindling is accelerated in rats with genetic predisposition to acoustic stimulus-induced seizures, Brain Res. 376: 412–415.
Schwartzkroin, P.A., 1984, Epileptogenesis in the immature CNS, in: Electrophysiology of Epilepsy (P.A. Schwartzkroin and H.V. Wheal, eds.), New York: Academic Press, pp. 389–412.
Sperber, E.F., and Moshé, S.L., 1988, Age-related differences in seizure susceptibility to flurothyl, Dev. Brain Res. 39: 295–297.
Sperber, E.F., Wong, B.Y., Wurpel, J.N.D., and Moshé, S.L., 1987, Nigral infusions of muscimol or bicuculline facilitate seizures in developing rats, Dev. Brain Res. 37: 243–250.
Sperber, E.F., Brown, L.L., Wurpel, J.N.D., and Moshé, S.L., 1988, Nigral infusions of muscimol in rat pups produce local cerebral glucose utilization effects different from adult rats, Soc. Neu-rosci. Abstr. 14: 1296.
Sperber, E.F., Wurpel, J.N.D., and Moshé, S.L., 1989a, Evidence for the involvement of nigral GABAB receptors in seizures of rat pups, Dev. Brain Res. 47: 143–146.
Sperber, E.F., Wurpel, J.N.D., Zhao, D.Y., and Moshé, S.L., 1989b, Evidence for the involvement of nigral GABAA receptors in seizures of adult rats, Brain Res. 480: 378–382.
Sperber, E.F., Wurpel, J.N.D., Sharpless, N.S., and Moshé, S.L., 1989c, Intranigral GABAergic drug effects on striatal dopamine activity, Pharmacol. Biochem. Behav. 32: 1067–1070.
Toussi, H.R., Schatz, R.A., and Wasczak, B.L., 1987, Suppression of methionine sulfoximine seizures by intranigral gamma-vinyl GABA injection, Eur. J. Pharmacol. 37: 261–264.
Turski, L., Cavalheiro, E.A., Schwarz, M., Turski, W.A., Mello, L.E.A.M., Bartolotto, Z.A., Klockgether, T., and Sontag, K.H., 1986, Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma-vinyl GABA in the substantia nigra, Brain Res. 370: 294–309.
Unerstall, J.R., Kuhar, M.J., Niehoff, D.L., and Palacios, J.M., 1981, Benzodiazepine receptors are coupled to a subpopulation of GABA receptors: Evidence from a quantiative autoradiographic study, J. Pharmacol. Exp. Ther. 218: 797–804.
Veening, J.G., Cornelissen, F.M., and Lieven, P.A.J.M., 1980, The topical organization of the afferents to the caudoputamen in rat: A horse-radish peroxidase study, Neuroscience 5: 1253–1268.
Wada, J.A., and Sato, M., 1974, Generalized convulsive seizures induced by daily stimulation of the amygdala in cats, Neurology 24: 565–574.
Wamsley, J.K., Mc Cabe, R.T., and Gehlert, D.R., 1988, Autoradiographic localization of binding sites in several GABA and benzodiazepine receptor complexes, in: GABA and Benzodiasepine Receptors (R.F. Squires, ed.), Boca Raton, FL: CRC Press, pp. 80–90.
Waszczak, B.L., Eng, N., and Walters, J., 1980, Effects of muscimol and Picrotoxin on single unit activity of substantia nigra neurons, Brain Res. 188: 185–197.
Wong, B.Y., and Mosh, S.L., 1987, Mutual interactions between repeated flurothyl convulsions and electrical kindling, Epilepsy Res. 1: 159–64.
Woodbury, L.A., 1977, Incidence and prevalence of seizure disorders including the epilepsies in the U.S.A. A review and analysis of the literature, in: Plan for the Nationwide Action of Epilepsy, (NIH) DHEW Publication No., pp. 78–276; IV:24-77.
Wurpel, J.N.D., Sperber, E.F., and Moshé, S.L., 1988a, Infusions of an excitatory aminoacid antagonist into the substantia nigra evoke an age-dependent effect on seizures, Soc. Neurosci. Abstr. 14: 1148.
Wurpel, J.N.D., Tempel, A., Sperber, E.F., and Moshé, S.L., 1988b, Age-related changes of muscimol binding in the substantia nigra, Dev. Brain Res. 43: 305–308.
Wurpel, J.N.D., Sperber, E.F., and Moshé, S.L., 1989, Baclofen inhibits kindling in immature rat, Epilepsy Res. (in press).
Yamasaki, D.S., Krautharner, G.M., and Rhoades, R.W., 1986, Superior collicular projection to intralaminar thalamus in the rat, Brain Res. 378: 223–33.
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Moshé, S.L., Sperber, E.F. (1990). Substantia Nigra-Mediated Control of Generalized Seizures. In: Avoli, M., Gloor, P., Kostopoulos, G., Naquet, R. (eds) Generalized Epilepsy. Birkhäuser Boston. https://doi.org/10.1007/978-1-4684-6767-3_25
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