Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-17T14:36:04.196Z Has data issue: false hasContentIssue false
  • English
  • Français

Cholinergic Mechanisms in Generalized Seizures: Importance of the Zona Incerta

Published online by Cambridge University Press:  18 September 2015

Stefan M. Brudzynski ,
James W. Cruickshank  and
Richard S. McLachlan
Stefan M. Brudzynski*
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario, and Epilepsy Research Laboratory, University Hospital, London
James W. Cruickshank
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario, and Epilepsy Research Laboratory, University Hospital, London
Richard S. McLachlan
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario, and Epilepsy Research Laboratory, University Hospital, London
*
Department of Clinical Neurological Sciences, University Hospital, P.O. Box 5339, Postal Stn. A, London, Ontario, Canada N6A 5A5
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective:

Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain.

Methods:

Carbachol was injected directly into the brain in a dose of 1 or 3 (jg. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe.

Results:

Injections of high dose carbachol (3 (jg) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 ug) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta.

Conclusions:

Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 22 , Issue 2 , May 1995 , pp. 116 - 120
Copyright
Copyright © Canadian Neurological Sciences Federation 1995

References

1.Beleslin, DB., Grbovic, L., Radmanovic, BZ.The pharmacology of gross behavioural effects of cholinomimetic substances injected into the cerebral ventricles of unanesthetized cats: evidence for central muscarinic mediation. Neuropharmacology 1974; 13: 1163–1169.CrossRefGoogle Scholar
2.Beleslin, DB., Samardzic, R.Comparative study of aggressive behaviour after injection of cholinomimetics, anticholinesterases, nicotine, and muscarinic ganglionic stimulants into the cerebral ventricles of conscious cats: failure of nicotinic drugs to evoke aggression. Psychopharmacology 1979; 60: 147–153.CrossRefGoogle Scholar
3.Cohen, SL., Morley, BJ., Snead, OC.An EEG analysis of convulsive activity produced by cholinergic agents. Prog Neuro-psychopharmacol 1981; 5: 383–388.CrossRefGoogle ScholarPubMed
4.Lundy, PM., Shaw, RK.Modification of cholinergically-induced convulsive activity and cyclic GMP levels in the CNS. Neuropharmacology 1983; 22: 55–63.CrossRefGoogle ScholarPubMed
5.Olney, JW., deGubareff, T., Labruyere, J.Seizure-related brain damage induced by cholinergic agents. Nature 1983; 301: 520–522.CrossRefGoogle ScholarPubMed
6.Spehlmann, R., Daniels, JC., Chnag, CM.Acetylcholine and the epileptiform activity of chronically isolated cortex. Arch Neurol 1971; 24: 401–407.CrossRefGoogle ScholarPubMed
7.Turski, WA., Cavalheiro, EA., Schwarz, M., et al. Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav Brain Res 1983; 9: 315–335.CrossRefGoogle ScholarPubMed
8.Turski, WA., Czuczwar, SJ., Turski, L., Kleinrok, Z.Systemic pilocarpine produces limbic seizures and brain damage in mice. Neurosci Lett 1983; 14: 380S.Google Scholar
9.McDonough, JH., Shih, T-M.Cholinergic modulation of somaninduced seizures. Soc Neurosci Abstr 1991; 17: 1607.Google Scholar
10.Wasterlain, CG., Jonec, V.Muscarinic kindling: transsynaptic generation of a chronic seizure focus. Life Sci 1980; 26: 387–391.CrossRefGoogle ScholarPubMed
11.Grossman, SP.Chemically induced epileptiform seizures in the cat. Science 1963; 142: 409–411.CrossRefGoogle ScholarPubMed
12.Snead, OC. III. Seizures induced by carbachol, morphine, and leucine-encephalin: a comparison. Ann Neurol 1983; 13: 445–451.CrossRefGoogle Scholar
13.Turski, WA., Cavalheiro, EA., Turski, L., Kleinrok, Z.Intrahippocampal betanechol in rats: behavioural, electroencephalographic and neuropathological correlates. Behav Brain Res 1983; 7: 361–370.CrossRefGoogle Scholar
14.Cain, DP.Bidirectional transfer of electrical and carbachol kindling. Brain Res 1983; 260: 135–138.CrossRefGoogle ScholarPubMed
15.Connor, JD., Rossi, GV., Baker, WW.Characteristics of tremor in cats following injections of carbachol into the caudate nucleus. Exp Neurol 1966; 14: 371–382.CrossRefGoogle ScholarPubMed
16.Decsi, L., Nagy, J.Chemical stimulation of the amygdala with special regard to influence on the hypothalamus. Neuropharmacology 1974; 13: 1153–1162.CrossRefGoogle ScholarPubMed
17.Elazar, Z.Epileptogenic effects of carbachol microinjected in the brainstem. Soc Neurosci Abstr 1985; 11: 1314.Google Scholar
18.Elazar, Z., Feldman, Z.Brainstem experimental seizures produced by microinjections of carbachol. Epilepsia 1987; 28: 463–470.CrossRefGoogle ScholarPubMed
19.Piredda, S., Gale, K.A crucial epileptogenic site in the deep prepiriform cortex. Nature 1985; 317: 623–625.CrossRefGoogle ScholarPubMed
20.Stivers, JA., Skirboll, LR., Long, R., Crawley, JN.Anatomical analysis of frontal cortex sites at which carbachol induced seizures in the rat. Pharmacol Biochem Behav 1988; 30: 129–136.CrossRefGoogle ScholarPubMed
21.McLachlan, RS., Brudzynski, SM., Bihari, F.EEG and behavioural effects of carbachol in the anterior hypothalamic/preoptic area of the basal forebrain. Epilepsia 1987; 28: 632–633.Google Scholar
22.Mraovitch, S., Calando, Y., Goadsby, PJ., Seylaz, J.Cholinergic stimulation of the ventroposterior thalamic nucleus induces limbic seizures: behavioral, ECoG, and metabolic correlates. Soc Neurosci Abstr 1991; 17: 175.Google Scholar
23.Canadian Council on Animal Care, Guide to the Care and use of Experimental Animals, vol. 1, Ottawa, Ontario: CCAC, 1984, 120.Google Scholar
24.Paxinos, G., Watson, C.The Rat Brain in Stereotaxic Coordinates, 2nd ed., Sydney: Academic Press, 1986.Google Scholar
25.Brudzynski, SM., McLachlan, RS., Girvin, JP.Cholinergically mediated reduction of locomotor activity from the basal forebrain in the rat. Exp Neurol 1989; 105: 197–205.CrossRefGoogle ScholarPubMed
26.Myers, RD.Handbook of Drug and Chemical Stimulation of the Brain. Behavioral, Pharmacological and Physiological Aspects, New York: Van Rostrand-Reinhold, 1974: 759.Google Scholar
27.Nashold, BS Jr, Gills, JP Jr. Chemical stimulation of telencephalon, diencephalon and mesencephalon in unrestrained animals. J Neuropathol Exp Neurol 1960; 19: 580–590.CrossRefGoogle Scholar
28.Burnham, WM.Core mechanisms in generalized convulsions. Fed Proc 1985; 44: 2442–2445.Google ScholarPubMed
29.Gioanni, Y., Gioanni, H., Mitrovic, N.Seizures can be triggered by stimulating non-cortical structures in the quaking mutant mouse. Epilepsy Res 1991; 9: 19–31.CrossRefGoogle ScholarPubMed
30.Villablanca, J., Schlag, J., Marcus, R.Blocking of experimental spike and wave by a localized forebrain lesion. Epilepsia 1970; II: 163–177.CrossRefGoogle Scholar
31.Kaelber, WW., Smith, TB.Projections of the zona incerta in the cat, with stimulation controls. Exp Neurol 1979; 63: 177–200.CrossRefGoogle ScholarPubMed
32.Ricardo, JA.Efferent connections of the subthalamic region in the rat. II. The zona incerta. Brain Res 1981; 214: 43–60.CrossRefGoogle ScholarPubMed
33.McLachlan, RS., Bihari, F.Secondary generalization of seizures from a cortical penicillin focus following stimulation of the basal forebrain. Exp Neurol 1990; 109: 237–242.CrossRefGoogle ScholarPubMed
34.Browning, R., Maggio, R., Sahibzada, N., Gale, K.Role of brainstem structures in seizures initiated from the deep prepiriform cortex of rats. Epilepsia 1993; 34: 393–407.CrossRefGoogle ScholarPubMed
35.Magistris, MR., Mouradian, MS., Gloor, P.Generalized convulsions induced by pentylenetetrazol in the cat: participation of forebrain, brainstem, and spinal cord. Epilepsia 1988; 29: 379–388.CrossRefGoogle ScholarPubMed
36.Jacobowitz, DM., Palkovits, M.Topographic atlas of catecholamine and acetylcholinesterase-containing neurons in the rat brain. J Comp Neurol 1974; 157: 13–28.CrossRefGoogle ScholarPubMed
37.Kimura, H., McGeer, PL., Peng, JH., McGeer, EG.The central cholinergic system studied by choline acetyltransferase immunohisto-chemistry in the cat. J Comp Neurol 1981; 200: 151–201.CrossRefGoogle Scholar
38.Cruickshank, JW., Brudzynski, SM., McLachlan, RS.Involvement of Ml muscarinic receptors in the initiation of cholinergically induced epileptic seizures in the rat brain. Brain Res 1994; 643: 125–129.CrossRefGoogle ScholarPubMed