Modulation of Network Activity in Dissociated Hippocampal Cultures by Enzymatic Digestion of Extracellular Matrix
To investigate the role of extracellular matrix in spontaneous neuronal network activity, we used microelectrode array technology and enzymatic treatment of hippocampal culture with hyaluronidase, which digests the major component of extracellular matrix, hyaluronic acid. Studies were performed using hippocampal cells that were dissociated from embryonic С57ВL6 mice (E18) and plated on microelectrode arrays (MEAs). Our findings revealed that hyaluronidase promoted seizure-like activity during two weeks after the beginning of hyaluronidase treatment in 17th day in vitro: the treatment transformed the normal network bursts to “superbursts”, which lasted about 25–35 seconds. These superbursts appeared on the third day after hyaluronidase treatment with intersuperburst interval of 1–3 minutes. Seizure-like activity in hyaluronidase-treated cultures was irreversible during 2 weeks, but could be suppressed by an L-VGCC blocker and by an AMPA receptor antagonist. These results suggest that the changes in expression of hyaluronic acid can be epileptogenic and provide an in vitro model for dissection of the underlying mechanisms.
- Dityatev A. Remodeling of extracellular matrix and epileptogenesis. Epilepsia 2010; 51: 61–65.
- Galtrey C.M., Fawcett J.W. The role of chondroitin sulfate proteoglycans in regeneration and plasticity in the central nervous system. Brain Res Rev 2007; 54: 1–18.
- Kwok J.C., Dick G., Wang D., Fawcett J.W. Extracellular matrix and perineuronal nets in CNS repair. Dev Neurobiol 2011; 71: 1073–1089.
- Kochlamazashvili G., Henneberger C., Bukalo O., Dvoretskova E., Senkov O., Lievens P.M.-J., Westenbroek R., Engel A.K., Catterall W.A., Rusakov D., Schachner M., Dityatev A. The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca2+ channels. Neuron 2010; 67: 116–128.
- Frischknecht R., Heine M., Perrais D., Seidenbecher C.I., Choquet D., Gundelfinger E.D. Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity. Nat Neurosci 2009; 12: 897–904.
- Kochlamazashvili G., Senkov O., Grebenyuk S., Robinson C., Xiao M.F., Stummeyer K., Gerardy-Schahn R., Engel A.K., Feig L., Semyanov A., Suppiramaniam V., Schachner M., Dityatev A. Neural cell adhesion molecule-associated polysialic acid regulates synaptic plasticity and learning by restraining the signaling through GluN2B-containing NMDA receptors. Neurosci 2010; 30: 4171–4183.
- Kalachikov S., Evgrafov O., Ross B., Winawe M., Barker-Cummings C., Martinelli Boneschi F., Choi C., Morozov P., Das K., Teplitskaya E., Yu A., Cayanis E., Penchaszadeh G., Kottmann A.H., Pedley T.A., Hauser W.A., Ottman R., Gilliam T.C. Mutations in LGI1 causeautoso-mal-dominant partial epilepsy with auditory features. Nat Genet 2002; 30: 335–341.
- Powell E.M., Campbell D.B., Stanwood G.D., Davis C., Noebels J.L., Levitt P. Genetic disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy and behavioral dysfunction. J Neurosci 2003; 23: 622–631.
- Isom L.L. Beta subunits: players in neuronal hyperexcitability? Novartis Found Symp 2002; 241: 124–138.
- Vedunova M.V., Korotchenko S.A., Balashova A.N., Isakova A.O., Khaspekov L.G., Kazantsev V.B., Mukhina I.V. Sovrem Technol Med 2011; 2: 7–13.
- Pimashkin А., Kastalskiy I., Simonov A., Koryagina A., Mukhina I., Kazantsev V. Spiking signatures of spontaneous activity bursts in hippocampal cultures. Front Comput Neurosci 2011; 5: 46.
- Giamanco K.A., Morawski M., Matthews R.T. Perineuronal net formation and structure in aggrecan knockout mice. Neuroscience 2010; 170(4): 1314–1327.
- Frischknecht R., Seidenbecher C.I. The crosstalk of hyaluronan-based extracellular matrix and synapses. Neuron Glia Biol 2008; 4(3): 249–257.
- Bruckner G., Grosche J., Schmidt S., Hartig W., Margolis R.U., Delpech B., Seidenbecher C.I., Czaniera R., Schachner M. Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R. J Comp Neurol 2000; 428(4): 616–629.
