Startseite Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

  • Iryna Hlushchenko und Pirta Hotulainen EMAIL logo
Veröffentlicht/Copyright: 8. Juli 2019

Abstract

Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

Acknowledgments

We thank Seija Lågas, Outi Nikkilä, Rimante Minkeviciene and Amr Abouelezz for their help with neuronal culture preparation. We are grateful to Amr Abouelezz for the English proofreading. All imaging was performed using microscopes in the Biomedicum Imaging Unit of University of Helsinki. This work was supported by the CIMO (IH/PH), Kordelin Foundation (IH), Minerva Foundation (IH/PH), Instrumentarium Foundation (PH), Academy of Finland (PH, SA 266351).

  1. Conflict of interest statement: The authors declare no competing financial interests.

References

Abraham, W.C. (2008). Metaplasticity: tuning synapses and networks for plasticity. Nat. Rev. Neurosci. 9, 387.10.1038/nrn2356Suche in Google Scholar

Anderson, R.G., Falck, J.R., Goldstein, J.L., and Brown, M.S. (1984). Visualization of acidic organelles in intact cells by electron microscopy. Proc. Natl. Acad. Sci. U.S.A. 81, 4838–4842.10.1073/pnas.81.15.4838Suche in Google Scholar

Bertling, E., Ludwig, A., Koskinen, M., and Hotulainen, P. (2012). Methods for three-dimensional analysis of dendritic spine dynamics. Methods Enzymol. 506, 391–406.10.1016/B978-0-12-391856-7.00043-3Suche in Google Scholar

Burkel, B.M., von Dassow, G., and Bement, W.M. (2007). Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin. Cell Motil. Cytoskeleton 64, 822–832.10.1002/cm.20226Suche in Google Scholar

Chen, C.-C., Lu, J., and Zuo, Y. (2014). Spatiotemporal dynamics of dendritic spines in the living brain. Front. Neuroanat. 8, 28.10.3389/fnana.2014.00028Suche in Google Scholar

Cooper, J.A., Loftus, D.J., Frieden, C., Bryan, J., and Elson, E.L. (1988). Localization and mobility of gelsolin in cells. J. Cell Biol. 106, 1229–1240.10.1083/jcb.106.4.1229Suche in Google Scholar

Fitzjohn, S.M., Pickard, L., Duckworth, J.K., Molnar, E., Henley, J.M., Collingridge, G.L., and Noël, J. (2001). An electrophysiological characterisation of long-term potentiation in cultured dissociated hippocampal neurones. Neuropharmacology 41, 693–699.10.1016/S0028-3908(01)00128-9Suche in Google Scholar

Forscher, P. (1989). Calcium and polyphosphoinositide control of cytoskeletal dynamics. Trends Neurosci. 12, 468–474.10.1016/0166-2236(89)90098-2Suche in Google Scholar

Fujii, S., Tanaka, H., and Hirano, T. (2018). Suppression of AMPA receptor exocytosis contributes to hippocampal LTD. J. Neurosci. 38, 5523–5537.10.1523/JNEUROSCI.3210-17.2018Suche in Google Scholar PubMed PubMed Central

Furukawa, K., Fu, W., Li, Y., Witke, W., Kwiatkowski, D.J., andMattson, M.P. (1997). The actin-severing protein gelsolin modulates calcium channel and NMDA receptor activities and vulnerability to excitotoxicity in hippocampal neurons. J. Neurosci. 17, 8178–8186.10.1523/JNEUROSCI.17-21-08178.1997Suche in Google Scholar

Halpain, S., Hipolito, A., and Saffer, L. (1998). Regulation of F-actin stability in dendritic spines by glutamate receptors and calcineurin. J. Neurosci. 18, 9835–9844.10.1523/JNEUROSCI.18-23-09835.1998Suche in Google Scholar

Hanson, J.E. and Madison, D.V. (2010). Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy. BMC Neurosci. 11, 96.10.1186/1471-2202-11-96Suche in Google Scholar

Hayama, T., Noguchi, J., Watanabe, S., Takahashi, N., Hayashi-Takagi, A., Ellis-Davies, G.C.R., Matsuzaki, M., and Kasai, H. (2013). GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling. Nat. Neurosci. 16, 1409–1416.10.1038/nn.3496Suche in Google Scholar

Hlushchenko, I., Koskinen, M., and Hotulainen, P. (2016). Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity. Cytoskeleton 73, 435–441.10.1002/cm.21280Suche in Google Scholar

Holtmaat, A. and Svoboda, K. (2009). Experience-dependent structural synaptic plasticity in the mammalian brain. Nat. Rev. Neurosci. 10, 647–658.10.1038/nrn2699Suche in Google Scholar

Hotulainen, P., Llano, O., Smirnov, S., Tanhuanpää, K., Faix, J., Rivera, C., and Lappalainen, P. (2009). Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J. Cell Biol. 185, 323–339.10.1083/jcb.200809046Suche in Google Scholar

Hu, H. and Hsueh, Y. (2014). Calcium influx and postsynaptic proteins coordinate the dendritic filopodium-spine transition. Dev. Neurobiol. 74, 1011–1029.10.1002/dneu.22181Suche in Google Scholar

Kinosian, H.J., Newman, J., Lincoln, B., Selden, L.A., Gershman, L.C., and Estes, J.E. (1998). Ca2+ regulation of gelsolin activity: binding and severing of F-actin. Biophys. J. 75, 3101–3109.10.1016/S0006-3495(98)77751-3Suche in Google Scholar

Kleppisch, T., Voigt, V., Allmann, R., and Offermanns, S. (2001). G(alpha)q-deficient mice lack metabotropic glutamate receptor-dependent long-term depression but show normal long-term potentiation in the hippocampal CA1 region. J. Neurosci. 21, 4943–4948.10.1523/JNEUROSCI.21-14-04943.2001Suche in Google Scholar

Li, Z., Jo, J., Jia, J., Lo, S., Whitcomb, D.J., Cho, K., and Sheng, M. (2010). Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell 141, 859–871.10.1016/j.cell.2010.03.053Suche in Google Scholar PubMed PubMed Central

Li, G.H., Arora, P.D., Chen, Y., McCulloch, C.A., and Liu, P. (2012). Multifunctional roles of gelsolin in health and diseases. Med. Res. Rev. 32, 999–1025.10.1002/med.20231Suche in Google Scholar

Lu, W., Man, H., Ju, W., Trimble, W.S., MacDonald, J.F., and Wang, Y.T. (2001). Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron 29, 243–254.10.1016/S0896-6273(01)00194-5Suche in Google Scholar

Malinow, R. and Malenka, R.C. (2002). AMPA receptor trafficking and synaptic plasticity. Annu. Rev. Neurosci. 25, 103–126.10.1146/annurev.neuro.25.112701.142758Suche in Google Scholar PubMed

Miesenböck, G., De Angelis, D.A., and Rothman, J.E. (1998). Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394, 192–195.10.1038/28190Suche in Google Scholar PubMed

Morishita, W., Marie, H., and Malenka, R.C. (2005). Distinct triggering and expression mechanisms underlie LTD of AMPA and NMDA synaptic responses. Nat. Neurosci. 8, 1043–1050.10.1038/nn1506Suche in Google Scholar PubMed

Moult, P.R., Gladding, C.M., Sanderson, T.M., Fitzjohn, S.M., Bashir, Z.I., Molnar, E., and Collingridge, G.L. (2006). Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. J. Neurosci. 26, 2544–2554.10.1523/JNEUROSCI.4322-05.2006Suche in Google Scholar PubMed PubMed Central

Nag, S., Larsson, M., Robinson, R.C., and Burtnick, L.D. (2013). Gelsolin: the tail of a molecular gymnast. Cytoskeleton 70, 360–384.10.1002/cm.21117Suche in Google Scholar PubMed

Okamoto, K.-I., Nagai, T., Miyawaki, A., and Hayashi, Y. (2004). Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat. Neurosci. 7, 1104–1112.10.1038/nn1311Suche in Google Scholar PubMed

Riedl, J., Crevenna, A.H., Kessenbrock, K., Yu, J.H., Neukirchen, D., Bista, M., Bradke, F., Jenne, D., Holak, T.A., Werb, Z., et al. (2008). Lifeact: a versatile marker to visualize F-actin. Nat. Methods 5, 605–607.10.1038/nmeth.1220Suche in Google Scholar PubMed PubMed Central

Sanderson, T.M., Collingridge, G.L., and Fitzjohn, S.M. (2011). Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs. Mol. Brain 4, 30.10.1186/1756-6606-4-30Suche in Google Scholar PubMed PubMed Central

Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012). Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682.10.1038/nmeth.2019Suche in Google Scholar PubMed PubMed Central

Schindelin, J., Rueden, C.T., Hiner, M.C., and Eliceiri, K.W. (2015). The ImageJ ecosystem: An open platform for biomedical image analysis. Mol. Reprod. Dev. 82, 518–529.10.1002/mrd.22489Suche in Google Scholar PubMed PubMed Central

Star, E.N., Kwiatkowski, D.J., and Murthy, V.N. (2002). Rapid turnover of actin in dendritic spines and its regulation by activity. Nat. Neurosci. 5, 239–246.10.1038/nn811Suche in Google Scholar PubMed

Tanaka, J. and Sobue, K. (1994). Localization and characterization of gelsolin in nervous tissues: gelsolin is specifically enriched in myelin-forming cells. J. Neurosci. 14, 1038–1052.10.1523/JNEUROSCI.14-03-01038.1994Suche in Google Scholar

Yang, S.-N., Tang, Y.-G., and Zucker, R.S. (1999). Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J. Neurophysiol. 81, 781–787.10.1152/jn.1999.81.2.781Suche in Google Scholar PubMed

Zhao, P. (2003). Gelsolin – a regulator of postsynaptic actin assembly and AMPA receptor expression (University of Basel), PhD Thesis. doi:10.5451/unibas-003354194.Suche in Google Scholar

Zheng, L., Baumann, U., and Reymond, J.-L. (2004). An efficient one-step site-directed and site-saturation mutagenesis protocol. Nucleic Acids Res. 32, e115.10.1093/nar/gnh110Suche in Google Scholar PubMed PubMed Central

Zhou, Q., Homma, K.J., and Poo, M. (2004). Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron 44, 749–757.10.1016/j.neuron.2004.11.011Suche in Google Scholar PubMed

Received: 2019-01-15
Accepted: 2019-06-06
Published Online: 2019-07-08
Published in Print: 2019-08-27

© 2019 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 25.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2019-0110/html
Button zum nach oben scrollen