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Published in: Brain Structure and Function 1/2004

01-04-2004 | Original Article

Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex

Authors: P. Flace, V. Benagiano, L. Lorusso, F. Girolamo, A. Rizzi, D. Virgintino, L. Roncali, G. Ambrosi

Published in: Brain Structure and Function | Issue 1/2004

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Abstract

‘Non-traditional’ large neurons of the granular layer of the cerebellar cortex include all its large neuronal types, except the Golgi neuron, which is instead one of the five ‘classic’ types of corticocerebellar neurons. The morphological, chemical and functional characteristics of the ‘non-traditional’ large neurons have not been entirely ascertained. The aim of this study was to ascertain whether morphological evidence can be provided of GABA synthesis within the ‘non-traditional’ large neurons of the human cerebellar cortex by means of immunocytochemistry for glutamic acid decarboxylase (GAD). Fragments of postmortem cerebellar cortex of various lobules from the hemispheres and vermis were studied. Immunoreactions revealed large neurons distributed throughout the granular layer in all lobules examined. They were discriminated by analyzing the morphological features of their bodies and processes and were identified as Golgi neurons and as some ‘non-traditional’ types, such as the candelabrum, Lugaro and synarmotic neurons. In addition, immunoreactive large neurons, with their bodies and processes closely adjacent to microvessels, were observed throughout the layer: these perivascular neurons could represent a new type of ‘non-traditional’ neuron of the cerebellar cortex. This study supplies the first indication that in the human cerebellar cortex some types of ‘non-traditional’ large neurons are GAD-immunoreactive, in addition to those neurons already known to be GABAergic (i.e., stellate, basket, Purkinje and Golgi neurons). These morphological data further point out possible functional roles for GABA as a neurotransmitter/neuromodulator in intrinsic, associative and projective circuits of the cerebellar cortex.
Literature
go back to reference Altman J, Bayer SA (1977) Time of origin and distribution of a new cell type in the rat cerebellar cortex. Exp Brain Res 29:265–274PubMed Altman J, Bayer SA (1977) Time of origin and distribution of a new cell type in the rat cerebellar cortex. Exp Brain Res 29:265–274PubMed
go back to reference Aoki E, Semba R, Kashiwamata S (1986) New candidate for GABAergic neurons in the rat cerebellum: an immunocytochemical study with anti-GABA antibody. Neurosci Lett 68:267–271CrossRefPubMed Aoki E, Semba R, Kashiwamata S (1986) New candidate for GABAergic neurons in the rat cerebellum: an immunocytochemical study with anti-GABA antibody. Neurosci Lett 68:267–271CrossRefPubMed
go back to reference Benagiano V, Flace P, Virgintino D, Rizzi A, Roncali L, Ambrosi G (2000) Immunolocalization of glutamic acid decarboxylase in postmortem human cerebellar cortex. A light microscopy study. Histochem Cell Biol 114:191–195PubMed Benagiano V, Flace P, Virgintino D, Rizzi A, Roncali L, Ambrosi G (2000) Immunolocalization of glutamic acid decarboxylase in postmortem human cerebellar cortex. A light microscopy study. Histochem Cell Biol 114:191–195PubMed
go back to reference Benagiano V, Roncali L, Virgintino D, Flace P, Errede M, Rizzi A, Girolamo F, Robertson D, Bormann J, Ambrosi G (2001) GABA immunoreactivity in the human cerebellar cortex: a light and electron microscopical study. Histochem J 33:537–543CrossRefPubMed Benagiano V, Roncali L, Virgintino D, Flace P, Errede M, Rizzi A, Girolamo F, Robertson D, Bormann J, Ambrosi G (2001) GABA immunoreactivity in the human cerebellar cortex: a light and electron microscopical study. Histochem J 33:537–543CrossRefPubMed
go back to reference Braak H (1974) On the intermediate cells of Lugaro within the cerebellar cortex of man. A pigmentarchitectonic study. Cell Tiss Res 149:399–411 Braak H (1974) On the intermediate cells of Lugaro within the cerebellar cortex of man. A pigmentarchitectonic study. Cell Tiss Res 149:399–411
go back to reference Braak E, Braak H (1983) On three types of large nerve cells in the granular layer of the human cerebellar cortex. Anat Embryol 166:67–86PubMed Braak E, Braak H (1983) On three types of large nerve cells in the granular layer of the human cerebellar cortex. Anat Embryol 166:67–86PubMed
go back to reference Braak E, Braak H (1993) The new monodendritic neuronal type within the adult human cerebellar granule cell layer shows calretinin-immunoreactivity. Neurosci Lett 154:199–202CrossRefPubMed Braak E, Braak H (1993) The new monodendritic neuronal type within the adult human cerebellar granule cell layer shows calretinin-immunoreactivity. Neurosci Lett 154:199–202CrossRefPubMed
go back to reference Castejon OJ, Castejon HV (2000) Correlative microscopy of cerebellar Golgi cells. Biocell 24:13–30PubMed Castejon OJ, Castejon HV (2000) Correlative microscopy of cerebellar Golgi cells. Biocell 24:13–30PubMed
go back to reference Christ H (1985) Fusiform nerve cells of the granular layer in the cerebellar cortex of the baboon. Neurosci Lett 56:195–198CrossRefPubMed Christ H (1985) Fusiform nerve cells of the granular layer in the cerebellar cortex of the baboon. Neurosci Lett 56:195–198CrossRefPubMed
go back to reference Clements JR, Monaghan PL, Beitz AJ (1987) An ultrastructural description of glutamate-like immunoreactivity in the rat cerebellar cortex. Brain Res 421:343–348CrossRefPubMed Clements JR, Monaghan PL, Beitz AJ (1987) An ultrastructural description of glutamate-like immunoreactivity in the rat cerebellar cortex. Brain Res 421:343–348CrossRefPubMed
go back to reference Diño MR, Nunzi MG, Anelli R, Mugnaini E (2000) Distribution of unipolar brush cells of the vestibulocerebellum: afferents and targets. Prog Brain Res 124:123–137PubMed Diño MR, Nunzi MG, Anelli R, Mugnaini E (2000) Distribution of unipolar brush cells of the vestibulocerebellum: afferents and targets. Prog Brain Res 124:123–137PubMed
go back to reference Eccles JC, Ito M, Szentàgothai J (1967) The cerebellum as a neuronal machine. Springer, Berlin Heidelberg New York Eccles JC, Ito M, Szentàgothai J (1967) The cerebellum as a neuronal machine. Springer, Berlin Heidelberg New York
go back to reference Floris A, Diño M, Jacobowitz DM, Mugnaini E (1994) The unipolar brush cells of the rat cerebellar cortex and cochlear nucleus are calretinin-positive: a study by light and electron microscopic immunocytochemistry. Anat Embryol 189:495–520PubMed Floris A, Diño M, Jacobowitz DM, Mugnaini E (1994) The unipolar brush cells of the rat cerebellar cortex and cochlear nucleus are calretinin-positive: a study by light and electron microscopic immunocytochemistry. Anat Embryol 189:495–520PubMed
go back to reference Fortin M, Marchand R, Parent A (1998) Calcium-binding proteins in primate cerebellum. Neurosci Res 30:155–168CrossRefPubMed Fortin M, Marchand R, Parent A (1998) Calcium-binding proteins in primate cerebellum. Neurosci Res 30:155–168CrossRefPubMed
go back to reference Fox CA (1959) The intermediate cells of Lugaro in the cerebellar cortex of the monkey. J Comp Neurol 112:39–51PubMed Fox CA (1959) The intermediate cells of Lugaro in the cerebellar cortex of the monkey. J Comp Neurol 112:39–51PubMed
go back to reference Gabbott PL, Somogyi P, Stewart MG, Hamori J (1986) GABA-immunoreactive neurons in the rat cerebellum: a light and electron microscope study. J Comp Neurol 251:474–490PubMed Gabbott PL, Somogyi P, Stewart MG, Hamori J (1986) GABA-immunoreactive neurons in the rat cerebellum: a light and electron microscope study. J Comp Neurol 251:474–490PubMed
go back to reference Geurts FJ, Timmermans J-P, Shigemoto R, De Shutter E (2001) Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum. Neuroscience 104:499–512CrossRefPubMed Geurts FJ, Timmermans J-P, Shigemoto R, De Shutter E (2001) Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum. Neuroscience 104:499–512CrossRefPubMed
go back to reference Golgi C (1874) Sulla fina anatomia del cervelletto umano. In: Opera Omnia Chapter V, vol 1. Istologia Normale, Hoepli, Milan, pp 99–111 Golgi C (1874) Sulla fina anatomia del cervelletto umano. In: Opera Omnia Chapter V, vol 1. Istologia Normale, Hoepli, Milan, pp 99–111
go back to reference Gragera RR, Muniz E, Martinez-Rodriguez R (1993) Electron microscopic immunolocalization of GABA and glutamic acid decarboxylase in cerebellar capillaries and their microenvironment. Cell Mol Biol 39:809–817 Gragera RR, Muniz E, Martinez-Rodriguez R (1993) Electron microscopic immunolocalization of GABA and glutamic acid decarboxylase in cerebellar capillaries and their microenvironment. Cell Mol Biol 39:809–817
go back to reference Houk JC, Mugnaini E (2003) Cerebellum. In: Squire LR, Bloom FE, McConnell SK, Roberts JL, Spitzer NC, Zigmond MJ (eds) Fundamental Neuroscience. Elsevier, Amsterdam, pp 841–872 Houk JC, Mugnaini E (2003) Cerebellum. In: Squire LR, Bloom FE, McConnell SK, Roberts JL, Spitzer NC, Zigmond MJ (eds) Fundamental Neuroscience. Elsevier, Amsterdam, pp 841–872
go back to reference Jansen J, Brodal A (1958) Das Kleinhirn. In: Bargmann W (ed) Handbuch der Mikroskopischen Anatomie des Menschen, vol 4. Springer, Berlin Heidelberg New York, pp 91–149 Jansen J, Brodal A (1958) Das Kleinhirn. In: Bargmann W (ed) Handbuch der Mikroskopischen Anatomie des Menschen, vol 4. Springer, Berlin Heidelberg New York, pp 91–149
go back to reference Katsetos CD, Frankfurter A, Christakos S, Mancall EL, Vlachos IN, Urich H (1993) Differential localization of class III, beta-tubulin isotype and calbindin-D28 k defines distinct neuronal types in the developing human cerebellar cortex. J Neuropathol Exp Neurol 52:655–666 Katsetos CD, Frankfurter A, Christakos S, Mancall EL, Vlachos IN, Urich H (1993) Differential localization of class III, beta-tubulin isotype and calbindin-D28 k defines distinct neuronal types in the developing human cerebellar cortex. J Neuropathol Exp Neurol 52:655–666
go back to reference Lainé J, Axelrad H (1994) The candelabrum cell: a new interneuron in the cerebellar cortex. J Comp Neurol 339:159–173PubMed Lainé J, Axelrad H (1994) The candelabrum cell: a new interneuron in the cerebellar cortex. J Comp Neurol 339:159–173PubMed
go back to reference Lainé J, Axelrad H (1996) Morphology of the Golgi impregnated Lugaro cell in the rat cerebellar cortex: a reappraisal with a description of its axon. J Comp Neurol 375:618–640CrossRefPubMed Lainé J, Axelrad H (1996) Morphology of the Golgi impregnated Lugaro cell in the rat cerebellar cortex: a reappraisal with a description of its axon. J Comp Neurol 375:618–640CrossRefPubMed
go back to reference Lainé J, Axelrad H (1998) Lugaro cells target basket and stellate cells in the cerebellar cortex. Neuroreport 9:2399–2403PubMed Lainé J, Axelrad H (1998) Lugaro cells target basket and stellate cells in the cerebellar cortex. Neuroreport 9:2399–2403PubMed
go back to reference Landau E (1933) La cellule synarmotique dans le cervelet humain. Arch Anat 17:273–285 Landau E (1933) La cellule synarmotique dans le cervelet humain. Arch Anat 17:273–285
go back to reference Lugaro E (1894) Sulle connessioni tra gli elementi nervosi della corteccia cerebellare con considerazioni generali sul significato fisiologico dei rapporti tra gli elementi nervosi. Riv Sper Freniat 20:297–331 Lugaro E (1894) Sulle connessioni tra gli elementi nervosi della corteccia cerebellare con considerazioni generali sul significato fisiologico dei rapporti tra gli elementi nervosi. Riv Sper Freniat 20:297–331
go back to reference Melik-Musian AB, Fanardzhian VV (1998) Histological identification of Lugaro cells in the cat cerebellum. Neurosci Behav Physiol 28:1486–1489 Melik-Musian AB, Fanardzhian VV (1998) Histological identification of Lugaro cells in the cat cerebellum. Neurosci Behav Physiol 28:1486–1489
go back to reference Mugnaini E (1972) The histology and cytology of the cerebellar cortex. In: Larsell O, Jansen J (eds) The comparative anatomy and histology of the cerebellum: the human cerebellum, cerebellar connections and cerebellar cortex. Minnesota Press, Minneapolis, pp 201–264 Mugnaini E (1972) The histology and cytology of the cerebellar cortex. In: Larsell O, Jansen J (eds) The comparative anatomy and histology of the cerebellum: the human cerebellum, cerebellar connections and cerebellar cortex. Minnesota Press, Minneapolis, pp 201–264
go back to reference Mugnaini E (2000) GABAergic inhibition in the cerebellar system. In: Martin DL, Olsen RW (eds) GABA in the Nervous System: the view at fifty years. Lippincott, Philadelphia, pp 383–407 Mugnaini E (2000) GABAergic inhibition in the cerebellar system. In: Martin DL, Olsen RW (eds) GABA in the Nervous System: the view at fifty years. Lippincott, Philadelphia, pp 383–407
go back to reference Mugnaini E, Floris A (1994) The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex. J Comp Neurol 339:174–180PubMed Mugnaini E, Floris A (1994) The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex. J Comp Neurol 339:174–180PubMed
go back to reference Mugnaini E, Oertel WH (1985) An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In: Björklund A, Hökfelt T (eds) Handbook of Chemical Neuroanatomy, vol 4: GABA and Neuropeptides in the CNS - Part I. Elsevier, Vancouver, pp 436–608 Mugnaini E, Oertel WH (1985) An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In: Björklund A, Hökfelt T (eds) Handbook of Chemical Neuroanatomy, vol 4: GABA and Neuropeptides in the CNS - Part I. Elsevier, Vancouver, pp 436–608
go back to reference Müller T (1994) Large nerve cells with long axons in the granular layer and white matter of the murine cerebellum. J Anat 184:419–423PubMed Müller T (1994) Large nerve cells with long axons in the granular layer and white matter of the murine cerebellum. J Anat 184:419–423PubMed
go back to reference Munoz DG (1990) Monodendritic neurons: a cell type in the human cerebellar cortex identified by chromogranin A-like immunoreactivity. Brain Res 528:335–338CrossRefPubMed Munoz DG (1990) Monodendritic neurons: a cell type in the human cerebellar cortex identified by chromogranin A-like immunoreactivity. Brain Res 528:335–338CrossRefPubMed
go back to reference Nunzi MG, Birnstiel S, Bhattacharyya BJ, Slater NT, Mugnaini E (2001) Unipolar brush cell form a glutamatergic projection system within the mouse cerebellar cortex. J Comp Neurol 434:329–341PubMed Nunzi MG, Birnstiel S, Bhattacharyya BJ, Slater NT, Mugnaini E (2001) Unipolar brush cell form a glutamatergic projection system within the mouse cerebellar cortex. J Comp Neurol 434:329–341PubMed
go back to reference Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopy study. Brain Res 450:342–353CrossRefPubMed Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopy study. Brain Res 450:342–353CrossRefPubMed
go back to reference Palay SL, Chan-Palay V (1974) Cerebellar cortex. Cytology and organization. Springer, Berlin Heidelberg New York Palay SL, Chan-Palay V (1974) Cerebellar cortex. Cytology and organization. Springer, Berlin Heidelberg New York
go back to reference Pensa A (1931) Osservazioni e considerazioni sulla struttura della corteccia cerebellare dei mammiferi. Mem R Accad Naz Lincei, Sci Fis Mat Nat, ser VI 5:25–50 Pensa A (1931) Osservazioni e considerazioni sulla struttura della corteccia cerebellare dei mammiferi. Mem R Accad Naz Lincei, Sci Fis Mat Nat, ser VI 5:25–50
go back to reference Ramón y Cajal S (1911) Histologie du Système Nerveux de l’Homme et des Vertébrés, vol II. Maloine, Paris Ramón y Cajal S (1911) Histologie du Système Nerveux de l’Homme et des Vertébrés, vol II. Maloine, Paris
go back to reference Ribak CE, Vaughn JE, Saito K (1978) Immunocytochemical localization of glutamic acid decarboxylase in neuronal somata following colchicine inhibition of axonal transport. Brain Res 140:315–332CrossRefPubMed Ribak CE, Vaughn JE, Saito K (1978) Immunocytochemical localization of glutamic acid decarboxylase in neuronal somata following colchicine inhibition of axonal transport. Brain Res 140:315–332CrossRefPubMed
go back to reference Storm-Mathisen J, Lecknes AK, Bore AT, Vaalant JL, Edminson P, Haug FM, Ottersen OP (1983) First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301:517–520 Storm-Mathisen J, Lecknes AK, Bore AT, Vaalant JL, Edminson P, Haug FM, Ottersen OP (1983) First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301:517–520
go back to reference Voogd J, Glickstein M (1998) Anatomy of the cerebellum. Trends Neurosci 21:370–375PubMed Voogd J, Glickstein M (1998) Anatomy of the cerebellum. Trends Neurosci 21:370–375PubMed
Metadata
Title
Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex
Authors
P. Flace
V. Benagiano
L. Lorusso
F. Girolamo
A. Rizzi
D. Virgintino
L. Roncali
G. Ambrosi
Publication date
01-04-2004
Publisher
Springer-Verlag
Published in
Brain Structure and Function / Issue 1/2004
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-003-0374-x

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Acknowledgement to Reviewers

Acknowledgement to reviewers 2003