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Using comparative anatomy in the axotomy model to identify distinct roles for microglia and astrocytes in synaptic stripping

Published online by Cambridge University Press:  05 January 2012

Shozo Jinno  and
Jun Yamada
Shozo Jinno*
Affiliation:
Department of Developmental Molecular Anatomy, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Jun Yamada
Affiliation:
Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
*
Correspondence should be addressed to: Shozo Jinno, Department of Developmental Molecular Anatomy, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan phone: 81-92-642-6051 fax: 81-92-642-6202 email: sjnno@med.kyushu-u.ac.jp
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Abstract

The synaptic terminals' withdrawal from the somata and proximal dendrites of injured motoneuron by the processes of glial cells following facial nerve axotomy has been the subject of research for many years. This phenomenon is referred to as synaptic stripping, which is assumed to help survival and regeneration of neurons via reduction of synaptic inputs. Because there is no disruption of the blood–brain barrier or infiltration of macrophages, the axotomy paradigm has the advantage of being able to selectively investigate the roles of resident glial cells in the brain. Although there have been numerous studies of synaptic stripping, the detailed mechanisms are still under debate. Here we suggest that the species and strain differences that are often present in previous work might be related to the current controversies of axotomy studies. For instance, the survival ratios of axotomized neurons were generally found to be higher in rats than in mice. However, some studies have used the axotomy paradigm to follow the glial reactions and did not assess variations in neuronal viability. In the first part of this article, we summarize and discuss the current knowledge on species and strain differences in neuronal survival, glial augmentation and synaptic stripping. In the second part, we focus on our recent findings, which show the differential involvement of microglia and astrocytes in synaptic stripping and neuronal survival. This article suggests that the comparative study of the axotomy paradigm across various species and strains may provide many important and unexpected discoveries on the multifaceted roles of microglia and astrocytes in injury and repair.

Keywords

Axotomycomparative anatomyglial augmentationneuronal survivalsynaptic stripping
Type
Research Article
Information
Neuron Glia Biology , Volume 7 , Special Issue 1: The Physiological Function of Microglia , February 2011 , pp. 55 - 66
Copyright
Copyright © Cambridge University Press 2011

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References

REFERENCES

Adrian, E.K. Jr.Williams, M.G. and George, F.C. (1978) Fine structure of reactive cells in injured nervous tissue labeled with 3H-thymidine injected before injury. Journal of Comparative Neurology 180, 815–839.CrossRefGoogle ScholarPubMed
Aldskogius, H. (1978) Lipid accumulation in axotomized adult rabbit vagal neurons. Electron microscopical observations. Brain Research 140, 349–353.CrossRefGoogle ScholarPubMed
Aldskogius, H. (1982) Glial cell responses in the adult rabbit dorsal motor vagal nucleus during axon reaction. Neuropathology and Applied Neurobiology 8, 341–349.CrossRefGoogle ScholarPubMed
Aldskogius, H., Barron, K.D. and Regal, R. (1980) Axon reaction in dorsal motor vagal and hypoglossal neurons of the adult rat. Light microscopy and RNA-cytochemistry. Journal of Comparative Neurology 193, 165–177.CrossRefGoogle ScholarPubMed
Araque, A. and Perea, G. (2004) Glial modulation of synaptic transmission in culture. Glia 47, 241–248.Google Scholar
Arvidsson, J. and Aldskogius, H. (1982) Effect of repeated hypoglossal nerve lesions on the number of neurons in the hypoglossal nucleus of adult rats. Experimental Neurology 75, 520–524.CrossRefGoogle ScholarPubMed
Banati, R.B., Gehrmann, J., Schubert, P. and Kreutzberg, G.W. (1993) Cytotoxicity of microglia. Glia 7, 111–118.CrossRefGoogle ScholarPubMed
Barron, K.D. (2004) The axotomy response. Journal of Neurological Science 220, 119–121.CrossRefGoogle ScholarPubMed
Barron, K.D., Marciano, F.F., Amundson, R. and Mankes, R. (1990) Perineuronal glial responses after axotomy of central and peripheral axons. A comparison. Brain Research 523, 219–229.CrossRefGoogle ScholarPubMed
Biber, K., Neumann, H., Inoue, K. and Boddeke, H.W. (2007) Neuronal ‘On’ and ‘Off’ signals control microglia. Trends in Neurosciences 30, 596–602.Google Scholar
Blinzinger, K. and Kreutzberg, G. (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Zeitschrift für Zellforschung und Mikroskopische Anatomie 85 145–157.CrossRefGoogle ScholarPubMed
Blackburn, D., Sargsyan, S., Monk, P.N. and Shaw, P.J. (2009) Astrocyte function and role in motor neuron disease: a future therapeutic target? Glia 57, 1251–1264.CrossRefGoogle ScholarPubMed
Borke, R.C. (1982) Perisomatic changes in the maturing hypoglossal nucleus after axon injury. Journal of Neurocytology 11, 463–485.Google Scholar
Cajal, Y.R. (1928) Cajal's degeneration and regeneration of the nervous system. In DeFilipe, J. & Jones, E.G. (eds) History of Neuroscience No. 5. New York: Oxford University Press, 1991.Google Scholar
Cardona, A.E., Pioro, E.P., Sasse, M.E., Kostenko, V., Cardona, S.M., Dijkstra, I.M. et al. (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nature Neuroscience 9, 917–924.CrossRefGoogle ScholarPubMed
Carlson, J., Lais, A.C. and Dyck, P.J. (1979) Axonal atrophy from permanent peripheral axotomy in adult cat. Journal of Neuropathology and Experimental Neurology 38, 579–585.CrossRefGoogle ScholarPubMed
Castonguay, A., Lévesque, S. and Robitaille, R. (2001) Glial cells as active partners in synaptic functions. Progress in Brain Research 132, 227–240.Google Scholar
Chen, D.H. (1978) Qualitative and quantitative study of synaptic displacement in chromatolyzed spinal motoneurons of the cat. Journal of Comparative Neurology 177, 635–664.Google Scholar
Cova, J.L. and Aldskogius, H. (1986) Effect of axotomy on perineuronal glial cells in the hypoglossal and dorsal motor vagal nuclei of the cat. Experimental Neurology 93, 662–667.CrossRefGoogle ScholarPubMed
de Bilbao, F., Giannakopoulos, P., Srinivasan, A. and Dubois-Dauphin, M. (2000) In vivo study of motoneuron death induced by nerve injury in mice deficient in the caspase 1/ interleukin-1 beta-converting enzyme. Neuroscience 98, 573–583.CrossRefGoogle ScholarPubMed
Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S. et al. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 8, 752–758.CrossRefGoogle ScholarPubMed
Emirandetti, A., Graciele Zanon, R., Sabha, M. Jr. and de Oliveira, A.L. (2006) Astrocyte reactivity influences the number of presynaptic terminals apposed to spinal motoneurons after axotomy. Brain Research 1095, 35–42.CrossRefGoogle ScholarPubMed
Ferri, C.C., Ghasemlou, N., Bisby, M.A. and Kawaja, M.D. (2002) Nerve growth factor alters p75 neurotrophin receptor-induced effects in mouse facial motoneurons following axotomy. Brain Research 950, 180–185.CrossRefGoogle ScholarPubMed
Gowing, G., Vallières, L. and Julien, J.P. (2006) Mouse model for ablation of proliferating microglia in acute CNS injuries. Glia 53, 331–337.CrossRefGoogle ScholarPubMed
Graeber, M.B., Tetzlaff, W., Streit, W.J. and Kreutzberg, G.W. (1988) Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neuroscience Letters 85, 317–321.CrossRefGoogle Scholar
Graeber, M.B., Bise, K. and Mehraein, P. (1993) Synaptic stripping in the human facial nucleus. Acta Neuropathologica 86, 179–181.Google Scholar
Graeber, M.B. and Streit, W.J. (2010) Microglia: biology and pathology. Acta Neuropathologica 119, 89–105.CrossRefGoogle Scholar
Greensmith, L., Mentis, G.Z. and Vrbová, G. (1994) Blockade of N-methyl-D-aspartate receptors by MK-801 (dizocilpine maleate) rescues motoneurones in developing rats. Developmental Brain Research 81, 162–170.CrossRefGoogle ScholarPubMed
Halassa, M.M. and Haydon, P.G. (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annual Review of Physiology 72, 335–355.CrossRefGoogle ScholarPubMed
Haydon, P.G. (2001) GLIA: listening and talking to the synapse. Nature Reviews Neuroscience 2, 185–193.CrossRefGoogle Scholar
Horner, P.J. and Palmer, T.D. (2003) New roles for astrocytes: the nightlife of an ‘astrocyte’. La vida loca! Trends in Neurosciences 26, 597–603.CrossRefGoogle ScholarPubMed
Hornung, J.P., Koppel, H. and Clarke, P.G. (1989) Endocytosis and autophagy in dying neurons: an ultrastructural study in chick embryos. Journal of Comparative Neurology 283, 425–437.CrossRefGoogle ScholarPubMed
Hottinger, A.F., Azzouz, M., Déglon, N., Aebischer, P. and Zurn, A.D. (2000) Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus. Journal of Neuroscience 20, 5587–5593.Google Scholar
Huang, Y.H. and Bergles, D.E. (2004) Glutamate transporters bring competition to the synapse. Current Opinion in Neurobiology 14, 346–352.CrossRefGoogle Scholar
Jarosinski, K.W. and Massa, P.T. (2002) Interferon regulatory factor-1 is required for interferon-gamma-induced MHC class I genes in astrocytes. Journal of Neuroimmunology 122, 74–84.CrossRefGoogle ScholarPubMed
Johnson, I.P. and Duberley, R.M. (1998) Motoneuron survival and expression of neuropeptides and neurotrophic factor receptors following axotomy in adult and ageing rats. Neuroscience 84, 141–150.Google Scholar
Kiryu-Seo, S., Hirayama, T., Kato, R. and Kiyama, H. (2005) Noxa is a critical mediator of p53-dependent motor neuron death after nerve injury in adult mouse. Journal of Neuroscience 25, 1442–1447.Google Scholar
Kiryu-Seo, S., Gamo, K., Tachibana, T., Tanaka, K. and Kiyama, H. (2006) Unique anti-apoptotic activity of EAAC1 in injured motor neurons. EMBO Journal 25, 3411–3421.CrossRefGoogle ScholarPubMed
Kou, S.Y., Chiu, A.Y. and Patterson, P.H. (1995) Differential regulation of motor neuron survival and choline acetyltransferase expression following axotomy. Journal of Neurobiology 27, 561–572.Google Scholar
Koizumi, S. and Inoue, K. (1997) Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurons. British Journal of Pharmacology 122, 51–58.CrossRefGoogle Scholar
Koizumi, S., Fujishita, K., Tsuda, M., Shigemoto-Mogami, Y. and Inoue, K. (2003). Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures. Proceedings of the National Academy of Sciences of the U.S.A. 100, 11023–11028.CrossRefGoogle ScholarPubMed
Kuno, M. and Llinás, R. (1970) Alterations of synaptic action in chromatolysed motoneurones of the cat. Journal of Physiology 210, 823–838.CrossRefGoogle ScholarPubMed
Laiwand, R., Werman, R. and Yarom, Y. (1987) Time course and distribution of motoneuronal loss in the dorsal motor vagal nucleus of guinea pig after cervical vagotomy. Journal of Comparative Neurology 256, 527–537.Google Scholar
Laskawi, R. and Wolff, J.R. (1996) Changes in glial fibrillary acidic protein immunoreactivity in the rat facial nucleus following various types of nerve lesions. European Archives of Oto-Rhino-Laryngology 253, 475–480.CrossRefGoogle ScholarPubMed
Latov, N., Nilaver, G., Zimmerman, E.A., Johnson, W.G., Silverman, A.J., Defendini, R. et al. (1979) Fibrillary astrocytes proliferate in response to brain injury: a study combining immunoperoxidase technique for glial fibrillary acidic protein and radioautography of tritiated thymidine. Developmental Biology 72, 381–384.CrossRefGoogle ScholarPubMed
Lepore, A.C., Rauck, B., Dejea, C., Pardo, A.C., Rao, M.S., Rothstein, J.D. et al. (2008) Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nature Neuroscience 11, 1294–1301.CrossRefGoogle Scholar
Lindå, H., Hammarberg, H., Cullheim, S., Levinovitz, A., Khademi, M. and Olsson, T. (1998) Expression of MHC class I and beta2-microglobulin in rat spinal motoneurons: regulatory influences by IFN-gamma and axotomy. Experimental Neurology 150, 282–295.CrossRefGoogle ScholarPubMed
Lindå, H., Shupliakov, O., Ornung, G., Ottersen, O.P., Storm-Mathisen, J., Risling, M. et al. (2000) Ultrastructural evidence for a preferential elimination of glutamate-immunoreactive synaptic terminals from spinal motoneurons after intramedullary axotomy. Journal of Comparative Neurology 425, 10–23.Google Scholar
Lidman, O., Olsson, T. and Piehl, F. (1999) Expression of nonclassical MHC class I (RT1-U) in certain neuronal populations of the central nervous system. European Journal of Neuroscience 11, 4468–4472.CrossRefGoogle ScholarPubMed
Marchetti, B. and Abbracchio, M.P. (2005) To be or not to be (inflamed) – is that the question in anti-inflammatory drug therapy of neurodegenerative disorders? Trends in Pharmacological Sciences 26, 517–525.CrossRefGoogle ScholarPubMed
Martín, E.D., Fernández, M., Perea, G., Pascual, O., Haydon, P.G., Araque, A. et al. (2007) Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Glia 55, 36–45.CrossRefGoogle ScholarPubMed
Mattsson, P., Meijer, B. and Svensson, M. (1999) Extensive neuronal cell death following intracranial transection of the facial nerve in the adult rat. Brain Research Bulletin 49, 333–341.Google Scholar
Mentis, G.Z., Greensmith, L. and Vrbová, G. (1993) Motoneurons destined to die are rescued by blocking N-methyl-D-aspartate receptors by MK-801. Neuroscience 54, 283–285.Google Scholar
Moran, L.B. and Graeber, M.B. (2004) The facial nerve axotomy model. Brain Research Reviews 44, 154–178.CrossRefGoogle ScholarPubMed
Namikawa, K., Honma, M., Abe, K., Takeda, M., Mansur, K., Obata, T. et al. (2000) Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration. Journal of Neuroscience 20, 2875–2886.CrossRefGoogle ScholarPubMed
Nimmerjahn, A., Kirchhoff, F. and Helmchen, F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314–1318.CrossRefGoogle ScholarPubMed
Nissl, F. (1894) Uber eine neue Untersuchungsmethode des Centralorgans speziell zur Feststellung der Lokalisation der Nervenzellen. Zentralbl Nervenheilkd Psychiatr 17, 337–344.Google Scholar
Oh, C., Murray, B., Bhattacharya, N., Holland, D. and Tatton, W.G. (1994) (-)-Deprenyl alters the survival of adult murine facial motoneurons after axotomy: increases in vulnerable C57BL strain but decreases in motor neuron degeneration mutants. Journal of Neuroscience Research 38, 64–74.CrossRefGoogle ScholarPubMed
Oliet, S.H. and Poulain, D.A. (1999) Adenosine-induced presynaptic inhibition of IPSCs and EPSCs in rat hypothalamic supraoptic nucleus neurones. Journal of Physiology 520, 815–825.CrossRefGoogle ScholarPubMed
Oliveira, A.L., Thams, S., Lidman, O., Piehl, F., Hökfelt, T., Kärre, K. et al. (2004) A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy. Proceedings of the National Academy of Sciences of the U.S.A. 101, 17843–17848.Google Scholar
Panatier, A., Vallée, J., Haber, M., Murai, K.K., Lacaille, J.C. and Robitaille, R. (2011) Astrocytes are endogenous regulators of basal transmission at central synapses. Cell 146, 785–798.Google Scholar
Pekny, M. and Nilsson, M. (2005) Astrocyte activation and reactive gliosis. Glia 50, 427–434.Google Scholar
Perea, G., Navarrete, M. and Araque, A. (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends in Neurosciences 32, 421–431.CrossRefGoogle ScholarPubMed
Petitto, J.M., Huang, Z., Lo, J. and Streit, W.J. (2003) IL-2 gene knockout affects T lymphocyte trafficking and the microglial response to regenerating facial motor neurons. Journal of Neuroimmunology 134, 95–103.CrossRefGoogle ScholarPubMed
Purves, D. (1975) Functional and structural changes in mammalian sympathetic neurones following interruption of their axons. Journal of Physiology 252, 429–463.Google Scholar
Raivich, G., Moreno-Flores, M.T., Möller, J.C. and Kreutzberg, G.W. (1994) Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. European Journal of Neuroscience 6, 1615–1618.Google Scholar
Raivich, G., Bohatschek, M., Kloss, C.U., Werner, A., Jones, L.L. and Kreutzberg, G.W. (1999) Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Research Reviews 30, 77–105.Google Scholar
Rall, W. (1964) Theoretical significance of dendritic trees for neuronal input output relations. In Reiss, R. (ed.) Neural Theory and Modeling. Stanford: Stanford University Press.Google Scholar
Reisert, I., Wildemann, G., Grab, D. and Pilgrim, C. (1984) The glial reaction in the course of axon regeneration: a stereological study of the rat hypoglossal nucleus. Journal of Comparative Neurology 229, 121–128.Google Scholar
Sabha, M. Jr., Emirandetti, A.Cullheim, S. and De Oliveira, A.L. (2008) MHC I expression and synaptic plasticity in different mice strains after axotomy. Synapse 62, 137–148.Google Scholar
Sánchez-Vives, M.V. and Gallego, R. (1993) Effects of axotomy or target atrophy on membrane properties of rat sympathetic ganglion cells. Journal of Physiology 471, 801–815.CrossRefGoogle ScholarPubMed
Schelper, R.L. and Adrian, E.K. Jr. (1980) Non-specific esterase activity in reactive cells in injured nervous tissue labeled with 3H-thymidine or 125iododeoxyuridine injected before injury. Journal of Comparative Neurology 194, 829–844.Google Scholar
Schiefer, J., Kampe, K., Dodt, H.U., Zieglgänsberger, W. and Kreutzberg, G.W. (1999) Microglial motility in the rat facial nucleus following peripheral axotomy. Journal of Neurocytology 28, 439–453.Google Scholar
Schwartz, M., Butovsky, O., Brück, W. and Hanisch, U.K. (2006) Microglial phenotype: is the commitment reversible? Trends in Neurosciences 29, 68–74.Google Scholar
Serpe, C.J., Sanders, V.M. and Jones, K.J. (2000) Kinetics of facial motoneuron loss following facial nerve transection in severe combined immunodeficient mice. Journal of Neuroscience Research 62, 273–278.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Sjöstrand, J. (1965) Proliferative changes in glial cells during nerve regeneration. Zeitschrift für Zellforschung und Mikroskopische Anatomie 68, 481–493.CrossRefGoogle ScholarPubMed
Sjöstrand, J. (1971) Neuroglial proliferation in the hypoglossal nucleus after nerve injury. Experimental Neurology 30, 178–189.Google Scholar
Smith, M.E., Gibbs, M.A., Forno, L.S. and Eng, L.F. (1987) [3H]thymidine labeling of astrocytes in experimental allergic encephalomyelitis. Journal of Neuroimmunology 15, 309–321.CrossRefGoogle Scholar
Snider, W.D., Elliott, J.L. and Yan, Q. (1992) Axotomy-induced neuronal death during development. Journal of Neurobiology 23, 1231–1246.Google Scholar
Sofroniew, M.V. (1999) Neuronal responses to axotomy. In Tuszynski, M.H. & Kordower, J. (eds) CNS Regeneration: Basic Science and Clinical Advances. New York: Academic Press.Google Scholar
Søreide, A.J. (1981a) Variations in the axon reaction in animals of different ages. A light microscopic study on the facial nucleus of the rat. Acta Anatomica (Basel) 110, 40–47.Google Scholar
Søreide, A.J. (1981b) Variations in the perineuronal glial changes after different types of nerve lesion: light and electron microscopic investigations on the facial nucleus of the rat. Neuropathology and Applied Neurobiology 7, 195–204.Google Scholar
Sumner, B.E. and Sutherland, F.I. (1973) Quantitative electron microscopy on the injured hypoglossal nucleus in the rat. Journal of Neurocytology 2, 315–328.CrossRefGoogle ScholarPubMed
Sumner, B.E. (1979) Ultrastructural data, with special reference to bouton/glial relationships, from the hypoglossal nucleus after a second axotomy of the hypoglossal nerve. Experimental Brain Research 36, 107–118.Google Scholar
Svensson, M. and Aldskogius, H. (1993) Infusion of cytosine-arabinoside into the cerebrospinal fluid of the rat brain inhibits the microglial cell proliferation after hypoglossal nerve injury. Glia 7, 286–298.Google Scholar
Svensson, M., Mattsson, P. and Aldskogius, H. (1994) A bromodeoxyuridine labelling study of proliferating cells in the brainstem following hypoglossal nerve transection. Journal of Anatomy 185, 537–542.Google Scholar
Tetzlaff, W., Graeber, M.B., Bisby, M.A. and Kreutzberg, G.W. (1988) Increased glial fibrillary acidic protein synthesis in astrocytes during retrograde reaction of the rat facial nucleus. Glia 1, 90–95.CrossRefGoogle ScholarPubMed
Torvik, A. and Skjörten, F. (1971a) Electron microscopic observations on nerve cell regeneration and degeneration after axon lesions. I. Changes in the nerve cell cytoplasm. Acta Neuropathologica 17, 248–264.Google Scholar
Torvik, A. and Skjörten, F. (1971b) Electron microscopic observations on nerve cell regeneration and degeneration after axon lesions. II. Changes in the glial cells. Acta Neuropathologica 17, 265–282.Google Scholar
Torvik, A. and Søreide, A.J. (1975) The perineuronal glial reaction after axotomy. Brain Research 95, 519–529.CrossRefGoogle ScholarPubMed
Ulfhake, B. and Cullheim, S. (1988) Postnatal development of cat hind limb motoneurons. II: In vivo morphology of dendritic growth cones and the maturation of dendrite morphology. Journal of Comparative Neurology 278, 88–102.Google Scholar
van Rossum, D. and Hanisch, U.K. (2004) Microglia. Metabolic Brain Disease 19, 393–411.Google Scholar
Vilhardt, F. (2005) Microglia: phagocyte and glia cell. International Journal of Biochemistry and Cell Biology 37, 17–21.Google Scholar
Walz, W. (1989) Role of glial cells in the regulation of the brain ion microenvironment. Progress in Neurobiology 33, 309–333.CrossRefGoogle ScholarPubMed
Watson, W.E. (1972) Some quantitative observations upon the responses of neuroglial cells which follow axotomy of adjacent neurones. Journal of Physiology 225, 415–435.Google Scholar
Xin, L., Richardson, P.M., Gervais, F. and Skamene, E. (1990) A deficiency of axonal regeneration in C57BL/6J mice. Brain Research 510, 144–146.CrossRefGoogle ScholarPubMed
Yamada, J. and Jinno, S. (2011) Alterations in neuronal survival and glial reactions after axotomy by ceftriaxone and minocycline in the mouse hypoglossal nucleus. Neuroscience Letters 504, 295–300.CrossRefGoogle ScholarPubMed
Yamada, J., Hayashi, Y., Jinno, S., Wu, Z., Inoue, K., Kohsaka, S. et al. (2008) Reduced synaptic activity precedes synaptic stripping in vagal motoneurons after axotomy. Glia 56, 1448–1462.CrossRefGoogle ScholarPubMed
Yamada, J., Nakanishi, H. and Jinno, S. (2011) Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy. Neuroscience 182, 1–10.Google Scholar
Yu, W.H. (1988) Sex difference in neuronal loss induced by axotomy in the rat brain stem motor nuclei. Experimental Neurology 102, 230–235.CrossRefGoogle ScholarPubMed
Zhang, J.M., Wang, H.K., Ye, C.Q., Ge, W., Chen, Y., Jiang, Z.l. et al. (2003) ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40, 971–982.Google Scholar