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Intracortical grafts of embryonic basal forebrain tissue restore low voltage fast activity in rats with basal forebrain lesions

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Summary

Unilateral injections of kainic acid into the basal forebrain in a series of rats resulted in an increase in large amplitude slow waves, a correlated burst-suppression pattern of multi-unit activity, and a decrease in acetylcholinesterase staining in the neocortex ipsilateral to the kainic acid injection. Subsequently, a cell suspension, prepared from rat embryonic basal forebrain tissue, was injected adjacent to the recording electrodes ipsilateral to the kainic acid injection. This produced a gradual recovery of low voltage fast activity (LVFA) and a correlated continuous discharge pattern of multi-unit activity in the neocortex ipsilateral to the kainic acid injection. LVFA recovered more slowly at neocortical recording sites that received an injection of a cell suspension of hippocampal primordial cells or no injection at all. Acetylcholinesterase-positive fibers from the basal forebrain tissue invaded host cortex; no comparable outrgrowths were demonstrable in the hippocampal primordium tissue grafts. Restoration of cholinergic electrocortical activation may play an important role in the improvements in behavioral performance produced by basal forebrain grafts in the cortex in animals with basal forebrain lesions.

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References

  • Andersen P, Andersson SA (1968) Physiological basis of the alpha rhythm. Appleton-Century-Crofts, New York

    Google Scholar 

  • Angeleri F, Marchesi GF, Quattrini A (1969) Effects of chronic thalamic leisons on the electrical activity of the neocortex and on sleep. Arch Ital Biol 107:633–667

    Google Scholar 

  • Bigl V, Woolf NJ, Butcher LL (1982) Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis. Brain Res Bull 8:727–749

    Google Scholar 

  • Bonnet V, Bremer F (1937) Action de potassium, du calcium, et de l'acétylcholine sur les activités electriques, spontanées et provoquées de l'ecorce cerebrale. CR Soc Biol 126:1271–1275

    Google Scholar 

  • Bowen DM, Davison AN (1986) Biochemical studies of nerve cells and energy metabolism in Alzheimer's disease. Brit Med Bull 42:75–80

    Google Scholar 

  • Buzsáki G, Bickford RG, Ponomaref G, Thal LJ, Mandel R, Gage FH (1988) Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J Neurosci 8:4007–4026

    Google Scholar 

  • Buzsáki G, Gage FH, Czopf J, Björklund A (1987) Restoration of rhythmic slow activity (θ) in the subcortically denervated hippocampus by fetal CNS transplants. Brain Res 400:334–347

    Google Scholar 

  • Collerton D (1986) Cholinergic function and intellectual decline in Alzheimer's disease. Neurosci 19:1–28

    Google Scholar 

  • Cooley RK, Vanderwolf CH (1978) Construction of wire leads and electrodes for use in slow wave recording in small animals. Brain Res Bull 3:175–179

    Google Scholar 

  • Cuculic Z, Bost K, Himwich HE (1968) An examination of a possible cortical cholinergic link in the EEG arousal reaction. Progr Brain Res 28:27–39

    Google Scholar 

  • Davies P, Maloney AJF (1976) Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2:1403

    Google Scholar 

  • de Catanzaro D (1988) Practical statistics. Canadian Academic Technology, West Flanborough, Ontario, Canada

    Google Scholar 

  • Détári L, Vanderwolf CH (1987) Activity of identified cortically projecting and other basal forebrain neurones during large slow waves and cortical activation in anesthetized rats. Brain Res 437:1–8

    Google Scholar 

  • Dunnett SB, Toniolo G, Fine A, Ryan CN, Björklund A, Iversen, SD (1985) Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis-II sensorimotor and learning impairments. Neuroscience 16:787–797

    Google Scholar 

  • Fine A, Dunnett SB, Björklund A, Iversen SD (1985a) Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer disease. Proc Natl Acad Sci USA 82:5227–5230

    Google Scholar 

  • Fine A, Dunnett SB, Björklund A, Clarke D, Iversen SD (1985b) Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis. I. Biochemical and anatomical observations. Neuroscience 16:769–786

    Google Scholar 

  • Flicker C, Dean RL, Fisher SK, Bartus RT (1983) Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat. Pharmacol Biochem Behav 18:973–981

    Google Scholar 

  • Friedman E, Lever B, Kuster J (1983) Loss of cholinergic neurons in the rat neocortex produces deficits in passive avoidance learning. Pharmacol Biochem Behav 19:309–312

    Google Scholar 

  • Funderburk WH, Case TJ (1951) The effect of atropine on cortical potentials. Electroenceph Clin Neurophysiol 3:213–233

    Google Scholar 

  • Hepler DJ, Olton DS, Wenk GL, Coyle JT (1985a) Lesions in the nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments. J Neurosci 5:866–873

    Google Scholar 

  • Hepler DJ, Wenk GL, Cribbs BL, Olton DS, Coyle JT (1985b) Memory impairments following basal forebrain lesions. Brain Res 346:8–14

    Google Scholar 

  • Jasper HH, Tessier J (1970) Acetylcholine liberation from cerebral cortex during paradoxical (REM) sleep. Science 172:601–602

    Google Scholar 

  • Johnston MV, McKinney M, Coyle JT (1981) Neocortical-cholinergic innervation: a description of extrinsic and intrinsic components in the rat. Exp Brain Res 43:159–172

    Google Scholar 

  • Kanai T, Szerb JC (1965) Mesencephalic reticular activating system and cortical acetylcholine output. Nature (Lond) 205:80–82

    Google Scholar 

  • Koelle GB (1954) The histochemical localization of cholinesterase in the central nervous system of the rat. J Comp Neurol 100:211–228

    Google Scholar 

  • Lehmann J, Nagy JI, Atmadja S, Fibiger HC (1980) The nucleus basalis magnocellularis: The origin of a cholinergic projection to the neocortex of the rat. Neurosci 5:1161–1174

    Google Scholar 

  • Lerer B, Warner J, Friedman E, Vincent G, Gamzu E (1985). Cortical cholinergic impairment and behavioral deficits produced by kainic acid lesions of rat magnocellular basal forebrain. Behav Neurosci 99:661–677

    Google Scholar 

  • LoConte G, Bartolini L, Casamenti F, Marconcini-Pepeu I, Pepeu G (1982) Lesions of cholinergic forebrain nuclei: changes in avoidance behavior and scopolamine actions. Pharmacol Biochem Behav 17:933–937

    Google Scholar 

  • McKinney M, Coyle JT, Hedreen JC (1983) Topographic analysis of the innervation of the rat neocortex and hippocampus by the basal forebrain cholinergic system. J Comp Neurol 217:103–121

    Google Scholar 

  • Monnier M, Romanowski W (1961) Les systémes cholinoceptifs cérébraux-actions de l'acetylcholine, de la physostigmine, pilocarpine et de GABA. Electroenceph Clin Neurophysiol 14:486–500

    Google Scholar 

  • Murray CL, Fibiger HC (1986) Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis. Behav Neuroscience 100:23–32

    Google Scholar 

  • Phillis JW (1968) Acetylcholine release from the cerebral cortex: its role in cortical arousal. Brain Res 7:378–389

    Google Scholar 

  • Rye DB, Wainer BH, Mesulam MM, Mufson EJ, Saper CB (1984) Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience 13:627–643

    Google Scholar 

  • Salamone JD, Beart PM, Alpert JE, Iversen SD (1984) Impairment in T-maze reinforced alteration performance following nucleus basalis magnocellularis lesions in rats. Behav Brain Res 13:63–70

    Google Scholar 

  • Saper CB (1984) Organization of cerebral cortical afferent systems in the rat. II. Magnocellular basal nucleus. J Comp Neurol 222:313–342

    Google Scholar 

  • Schmidt RA, Björklund A, Stenevi V (1981) Intracerebral grafting of dissociated cell suspensions: a new approach for neuronal transplantation to deep brain sites. Brain Res 218:347–356

    Google Scholar 

  • Semba K, Szechtman H, Komisaruk BR (1980) Synchrony among rhythmical facial tremor, neocortical “alpha” waves, and thalamic non-sensory neuronal bursts in intact awake rats. Brain Res 195:281–298

    Google Scholar 

  • Sie G, Jasper HH, Wolfe L (1965) Rate of Ach release from cortical surface in encephale and cerveau isolé preparations in relation to arousal and epileptic activation of the ECoG. Electroenceph Clin Neurophysiol 18:206

    Google Scholar 

  • Siegel S (1956) Non-parametric statistics for the behavioral sciences. McGraw Hill, New York

    Google Scholar 

  • Spehlmann R, Norcross K (1982) Cholinergic mechanisms in the production of focal cortical slow waves. Experientia 38:109–111

    MathSciNet  MATH  Google Scholar 

  • Steriade M, Deschênes M (1984) The thalamus as a neuronal oscillator. Brain Res Rev 8:1–63

    Google Scholar 

  • Steriade M, Deschênes M, Domich L, Mulle C (1985) Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami. J Neurophysiol 54:1473–1497

    Google Scholar 

  • Stewart DJ, MacFabe DF, Vanderwolf CH (1984) Cholinergic activation of the electrocorticogram: role of the substantia innominata and effects of atropine and quinuclidinyl benzilate. Brain Res 322:219–232

    Google Scholar 

  • Szerb JC (1967) Cortical acetylcholine release and electroencephalographic arousal J Physiol 192:329–343

    Google Scholar 

  • Vanderwolf CH (1988) Cerebral activity and behavior: control by central cholinergic and serotonergic systems. Int Rev Neurobiol 30:225–340

    Google Scholar 

  • Vanderwolf CH, Stewart DJ (1988) Thalamic control of neocortical activation: a critical re-evaluation. Brain Res Bull 20:529–538

    Google Scholar 

  • Villablanca J, Salinas-Zeballos ME (1972) Sleep-wakefulness, EEG, and behavioral studies of chronic cats without the thalamus: the “athalamic cat.” Arch Ital Biol 110:383–411

    Google Scholar 

  • Wahle P, Sanides-Bucholtz C, Eckenstein F, Albus K (1984) Concurrent visualization of choline acetyltransferase-like immunoreactivity and retrograde transport of neocortically injected markers in basal forebrain neurons of cat and rat. Neurosci Lett 44:223–228

    Google Scholar 

  • Welner SA, Dunnett SB, Salamone JD, MacLean B, Iversen SD (1988) Transplantation of embryonic ventral forebrain grafts to the neocortex of rats with bilateral lesions of nucleus basalis magnocellularis ameliorates a lesion-induced deficit in spatial memory. Brain Res 463:192–197

    Google Scholar 

  • Wenk GL, Olton BS (1984) Recovery of neocortical choline acetyltransferase following ibotenic acid injection into the nucleus basalis of Meynert in rats. Brain Res 293:184–186

    Google Scholar 

  • Whishaw IQ, O'Connor WT, Dunnett SB (1985) Disruption of central cholinergic systems in the rat by basal forebrain lesions or atropine: effects on feeding, sensorimotor behaviour, locomotor activity, and spatial navigation. Behav Brain Res 17:103–115

    Google Scholar 

  • Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR (1982). Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239

    Google Scholar 

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Authors and Affiliations

  1. Department of Psychology, University of Western Ontario, N6A 5C2, London, Ontario, Canada

    C. H. Vanderwolf & R. K. Cooley

  2. Department of Physiology and Biophysics, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    A. Fine

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  1. C. H. Vanderwolf
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  2. A. Fine
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  3. R. K. Cooley
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Vanderwolf, C.H., Fine, A. & Cooley, R.K. Intracortical grafts of embryonic basal forebrain tissue restore low voltage fast activity in rats with basal forebrain lesions. Exp Brain Res 81, 426–432 (1990). https://doi.org/10.1007/BF00228136

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  • DOI: https://doi.org/10.1007/BF00228136

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