Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures

Abstract

The extracellular matrix (ECM) plays an important role in use-dependent synaptic plasticity. Hyaluronic acid (HA) is the backbone of the neural ECM, which has been shown to modulate α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptor mobility, paired-pulse depression, L-type voltage-dependent Ca2+ channel (L-VDCC) activity, long-term potentiation and contextual fear conditioning. To investigate the role of HA in the development of spontaneous neuronal network activity, we used microelectrode array recording and Ca2+ imaging in hippocampal cultures enzymatically treated with hyaluronidase. Our findings revealed an appearance of epileptiform activity 9 days after hyaluronidase treatment. The treatment transformed the normal network firing bursts and Ca2+ oscillations into long-lasting “superbursts” and “superoscillations” with durations of 11–100 s. The changes in Ca2+ transients in hyaluronidase-treated neurons were more prominent then in astrocytes and preceded changes in electrical activity. The Ca2+ superoscillations could be suppressed by applying the L-VDCC blocker diltiazem, whereas the neuronal firing superbursts could be additionally suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione as an antagonist of AMPA/kainate receptors. These results suggest that changes in the expression of HA can be epileptogenic and that hyaluronidase treatment in vitro provides a robust model for the dissection of the underlying mechanisms.

Modulation of network activity and induction of homeostatic synaptic plasticity by enzymatic removal of heparan sulfates

“…Interestingly, heparin binds L-VDCC [21]; moreover, another polyanionic glycan, hyaluronic acid, supports activity of L-VDCCs [22] and its enzymatic removal leads to appearance of epileptiform activity similar to that reported in this study [23]. Thus, modulation of L-VDCC activity can be one of the mechanisms by which a deficit of HSs induces HSP.…”

Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca2+ channels

“…This study demonstrated that application of hyaluronic acid to transfected CHO cells potentiated L-VDCC-mediated currents, while enzymatic digestion of hyaluronic acid with hyaluronidase impaired L-VDCC-mediated currents, Ca 2+ transients in dendritic spines, LTP and contextual fear conditioning (Kochlamazashvili et al, 2010). Hyaluronidase treatment led to appearance of long-lasting Ca 2+ transients and epileptiform bursts of neuronal activity in cultured hippocampal neurons grown on microelectrode arrays (Vedunova et al, 2013). …”

Biocompatibility of Bare Nanoparticles Based on Silicon and Gold for Nervous Cells

“…Dissociated hippocampal cells were taken from C57BL/6 mice embryos (E18) and cultured on coverslips during 14 days in vitro (DIV) according to the previously developed protocol [9]. The cell viability was maintained under constant conditions of 35.5 ∘ C, 5% CO 2 and a humidified atmosphere in a cell culture incubator.…”