Summary
Ultrastructural changes in hippocampal granule cells, mossy fibers and mossy fiber boutons were examined following the administration of picrotoxin in adult rats. Generalized seizures occurred within 5–10 min after the intraperitoneal injection of picrotoxin. The electron-microscopic examination of hippocampal tissues from rats that had been perfused with fixative during the seizure revealed that the large dense-core vesicles increased in number and accumulated on the presynaptic membranes of mossy fiber boutons; some of these vesicles appeared to be fused with the membranes, and omega-shaped exocytotic profiles were frequently seen. Furthermore, greatly increased numbers of coated vesicles (60–90 nm in diameter) were observed on the maturing faces of Golgi fields of granule cells. Thus, our study not only indicates an increased incidence of exocytosis of large dense-core vesicles during picrotoxin-induced seizures, but also suggests that these vesicles are replaced in excess from the perikaryon of the granule cell.
Similar content being viewed by others
References
Andres KH (1964) Mikropinozytose im Zentralnervensystem. Z Zellforsch 64:63–73
Bajorek JG, Lee RJ, Lomax P (1984) Neuropeptides: a role as endogenous mediators or modulators of epileptic phenomena. Ann Neurol 16 [Suppl]:531–538
Bircher RP, Kanai T, Wang SC (1962) Intravenous, cortical and intraventricular dose-effect relationship of pentylenetetrazol, picrotoxin and deslanoside in dogs. EEG Clin Neurophysiol 14:256–267
Bruggencate GT, Engberg I (1971) Iontophoretic studies in Deiters' nucleus of the inhibitory actions of GABA and related amino acids and the interactions of strychnine and picrotoxin. Brain Res 25:431–448
Eckenhoff MF, Pysh JJ (1979) Double-walled coated vesicle formation: evidence for massive and transient conjugate internalization of plasma membranes during cerebellar development. J Neurocytol 8:623–638
Gall C, Brecha N, Karten HJ, Chang K-J (1981) Localization of enkephalin-like immunoreactivity to identified axonal and neuronal population of the rat hippocampus. J Comp Neurol 198:335–350
Kanamatsu T, McGinty JF, Mitchell CL, Hong JS (1986) Dynorphin- and enkephalin-like immunoreactivity is altered in limbic-basal ganglia regions of rat brain after repeated electroconvulsive shock. J Neurosci 6:644–649
Kosaka T, Hama K, Wu, J-Y (1984) GABAergic synaptic boutons in the granule cell layer of rat dentate gyrus. Brain Res 293:353–359
Landis DMD, Reese TS (1974) Differences in membrane structure between excitatory and inhibitory synapses in the cerebellar cortex. J Comp Neurol 155:93–126
Lee RJ, Hong J-S, McGinty JF, Lomax P (1987) Increased enkephalin and dynorphin immunoreactivity in the hippocampus of seizure sensitive Mongolian gerbils. Brain Res 401:353–358
Löscher W (1982) Relationship between GABA concentrations in cerebrospinal fluid and seizure excitability. J Neurochem 38:293–295
McGinty JF, Henriksen SJ, Goldstein A, Terenius L, Bloom FE (1983) Dynorphin is contained within hippocampal mossy fibers: immunochemical alterations after kainic acid administration and colchicine-induced neurotoxicity. Proc Natl Acad Sci USA 80:589–593
McLean S, Rothman RB, Jacobson AE, Rice KC, Herkenham M (1987) Distribution of opiate receptor subtypes and enkephalin and dynorphin immunoreactivity in the hippocampus of squirrel, guinea pig, rat, and hamster. J Comp Neurol 255:497–510
Meldrum BS, Horton RW (1971) Convulsive effects of 4-deoxypyridoxine and of bicuculline in photosensitive baboons (Papio papio) and in rhesus monkeys (Macaca mulatta). Brain Res 35:419–436
Mihály A, Joó F, Szente M (1983) Neuropathological alterations in the neocortex of rats subjected to focal aminopyridine seizures. Acta Neuropathol 61:85–94
Morré DJ (1982) Intracellular vesicular transport: vesicles, guide elements and mechanisms. In: Weiss DG (ed) Axoplasmic transport, Springer, Berlin Heidelberg New York, pp 2–14
Nitsch C, Rinne U (1981) Large dense-core vesicle exocytosis and membrane recycling in the mossy fibre synapses of the rabbit hippocampus during epileptiform seizures. J Neurocytol 10:201–219
Olney JW, Rhee V, Ho OL (1974) Kainic acid; a powerful neurotoxin analogue of glutamate. Brain Res 77:507–512
Saito S, Tokunaga Y (1967) Some correlations between picrotoxininduced seizures and γ-aminobutyric acid in animal brain. J Pharmacol Exp Ther 157:546–554
Simmonds MA (1980) Evidence that bicuculline and picrotoxin act at separate sites to antagonize γ-aminobutyric acid in rat cuneate nucleus. Neuropharmacology 19:35–45
Stengaard-Pedersen K, Fredens K, Larsson L-I (1981) Enkephalin and zinc in the hippocampal mossy fiber system. Brain Res 212:230–233
Stengaard-Pedersen K, Fredens K, Larsson L-I (1983) Comparative localization of enkephalin and cholecystokinin immunoreactivities and heavy metals in the hippocampus. Brain Res 273:81–96
Storm-Mathisen J (1981) Glutamate in hippocampal pathways. Adv Biochem Psychopharmacol 27:43–55
Storm-Mathisen J, Iversen LL (1979) Uptake of [3H] glutamic acid in excitatory nerve endings: light and electronmicroscopic observations in the hippocampal formation of the rat. Neuroscience 4:1237–1253
Stone GC, Hammerschlag R, Bobinski JA (1984) Involvement of coated vesicles in the initiation of fast axonal transport. Brain Res 291:219–228
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Watanabe, H., Mizukawa, K. & Otsuka, N. Ultrastructural changes in granule cell somata and mossy fibers of the rat hippocampus during picrotoxin-induced convulsions. Cell Tissue Res. 255, 261–267 (1989). https://doi.org/10.1007/BF00224107
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00224107