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.