Bergmann glial ensheathment of dendritic spines regulates synapse number without affecting spine motility | Neuron Glia Biology | Cambridge Core (original) (raw)

Abstract

In the cerebellum, lamellar Bergmann glial (BG) appendages wrap tightly around almost every Purkinje cell dendritic spine. The function of this glial ensheathment of spines is not entirely understood. The development of ensheathment begins near the onset of synaptogenesis, when motility of both BG processes and dendritic spines are high. By the end of the synaptogenic period, ensheathment is complete and motility of the BG processes decreases, correlating with the decreased motility of dendritic spines. We therefore have hypothesized that ensheathment is intimately involved in capping synaptogenesis, possibly by stabilizing synapses. To test this hypothesis, we misexpressed GluR2 in an adenoviral vector in BG towards the end of the synaptogenic period, rendering the BG α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) Ca2+-impermeable and causing glial sheath retraction. We then measured the resulting spine motility, spine density and synapse number. Although we found that decreasing ensheathment at this time does not alter spine motility, we did find a significant increase in both synaptic pucta and dendritic spine density. These results indicate that consistent spine coverage by BG in the cerebellum is not necessary for stabilization of spine dynamics, but is very important in the regulation of synapse number.

References

Bourgeron, T. (2009) A synaptic trek to autism. Current Opinion in Neurobiology 19, 231–234.Google Scholar

Deng, J. and Dunaevsky, A. (2005) Dynamics of dendritic spines and their afferent terminals: spines are more motile than presynaptic boutons. Developmental Biology 277, 366–377.Google Scholar

Dunaevsky, A., Tashiro, A., Majewska, A., Mason, C. and Yuste, R. (1999) Developmental regulation of spine motility in the mammalian central nervous system. Proceedings of the National Academy of Sciences of the U.S.A. 96, 13438–13443.Google Scholar

Dunaevsky, A., Blazeski, R., Yuste, R. and Mason, C. (2001) Spine motility with synaptic contact. Nature Neuroscience 4, 685–686.Google Scholar

Fiala, J.C. and Harris, K.M. (2001) Extending unbiased stereology of brain ultrastructure to three-dimensional volumes. Journal of American Medical Information Association 8, 1–16.Google Scholar

Fiala, J.C., Kirov, S.A., Feinberg, M.D., Petrak, L.J., George, P., Goddard, C.A. et al. (2003) Timing of neuronal and glial ultrastructure disruption during brain slice preparation and recovery in vitro. Journal of Comparative Neurology 465, 90–103.Google Scholar

Grosche, J., Matyash, V., Moller, T., Verkhratsky, A., Reichenbach, A. and Kettenmann, H. (1999) Microdomains for neuron–glia interaction: parallel fiber signaling to Bergmann glial cells. Nature Neuroscience 2, 139–143.Google Scholar

Grosche, J., Kettenmann, H. and Reichenbach, A. (2002) Bergmann glial cells form distinct morphological structures to interact with cerebellar neurons. Journal of Neuroscience Research 68, 138–149.Google Scholar

Haber, M., Zhou, L. and Murai, K.K. (2006) Cooperative astrocyte and dendritic spine dynamics at hippocampal excitatory synapses. Journal of Neuroscience 26, 8881–8891.Google Scholar

Iino, M., Goto, K., Kakegawa, W., Okado, H., Sudo, M., Ishiuchi, S. et al. (2001) Glia-synapse interaction through Ca2+-permeable AMPA receptors in Bergmann glia. Science 292, 926–929.CrossRef Google Scholar PubMed

Korkotian, E. and Segal, M. (2001) Regulation of dendritic spine motility in cultured hippocampal neurons. Journal of Neuroscience 21, 6115–6124.Google Scholar

Kumar, V., Zhang, M.X., Swank, M.W., Kunz, J. and Wu, G.Y. (2005) Regulation of dendritic morphogenesis by Ras-PI3 K-Akt-mTOR and Ras-MAPK signaling pathways. Journal of Neuroscience 25, 11288–11299.Google Scholar

Lippman, J.J., Lordkipanidze, T., Buell, M.E., Yoon, S.O. and Dunaevsky, A. (2008) Morphogenesis and regulation of Bergmann glial processes during Purkinje cell dendritic spine ensheathment and synaptogenesis. Glia 56, 1463–1477.CrossRef Google Scholar PubMed

Murai, K.K., Nguyen, L.N., Irie, F., Yamaguchi, Y. and Pasquale, E.B. (2003) Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling. Nature Neuroscience 6, 153–160.Google Scholar

Nestor, M.W., Mok, L.P., Tulapurkar, M.E. and Thompson, S.M. (2007) Plasticity of neuron–glial interactions mediated by astrocytic EphARs. Journal of Neuroscience 27, 12817–12828.Google Scholar

Nishida, H. and Okabe, S. (2007) Direct astrocytic contacts regulate local maturation of dendritic spines. Journal of Neuroscience 27, 331–340.Google Scholar

Peters, A. and Kaiserman-Abramof, I.R. (1970) The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. American Journal of Anatomy 127, 321–355.Google Scholar

Sandsmark, D.K., Zhang, H., Hegedus, B., Pelletier, C.L., Weber, J.D. and Gutmann, D.H. (2007) Nucleophosmin mediates mammalian target of rapamycin-dependent actin cytoskeleton dynamics and proliferation in neurofibromin-deficient astrocytes. Cancer Research 67, 4790–4799.Google Scholar

Spacek, J. (1985) Three-dimensional analysis of dendritic spines. III. Glial sheath. Anatomy and Embryology 171, 245–252.CrossRef Google Scholar PubMed

Ventura, R. and Harris, K.M. (1999) Three-dimensional relationships between hippocampal synapses and astrocytes. Journal of Neuroscience 19, 6897–6906.Google Scholar

Volterra, A. and Meldolesi, J. (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nature Reviews. Neuroscience 6, 626–640.Google Scholar

Zepeda, R.C., Barrera, I., Castelan, F., Suarez-Pozos, E., Melgarejo, Y., Gonzalez-Mejia, E. et al. (2009) Glutamate-dependent phosphorylation of the mammalian target of rapamycin (mTOR) in Bergmann glial cells. Neurochemistry International 55, 282–287.Google Scholar