The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca2+ channels

Gaga Kochlamazashvili, Christian Henneberger, Olena Bukalo, Elena Dvoretskova, Oleg Senkov, Patricia M.J. Lievens, Ruth Westenbroek, Andreas K. Engel, William A. Catterall, Dmitri A. Rusakov, Melitta Schachner, Alexander Dityatev

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Although the extracellular matrix plays an important role in regulating use-dependent synaptic plasticity, the underlying molecular mechanisms are poorly understood. Here we examined the synaptic function of hyaluronic acid (HA), a major component of the extracellular matrix. Enzymatic removal of HA with hyaluronidase reduced nifedipine-sensitive whole-cell Ca2+ currents, decreased Ca2+ transients mediated by L-type voltage-dependent Ca2+ channels (L-VDCCs) in postsynaptic dendritic shafts and spines, and abolished an L-VDCC-dependent component of long-term potentiation (LTP) at the CA3-CA1 synapses in the hippocampus. Adding exogenous HA, either by bath perfusion or via local delivery near recorded synapses, completely rescued this LTP component. In a heterologous expression system, exogenous HA rapidly increased currents mediated by Cav1.2, but not Cav1.3, subunit-containing L-VDCCs, whereas intrahippocampal injection of hyaluronidase impaired contextual fear conditioning. Our observations unveil a previously unrecognized mechanism by which the perisynaptic extracellular matrix influences use-dependent synaptic plasticity through regulation of dendritic Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)116-128
Number of pages13
JournalNeuron
Volume67
Issue number1
DOIs
StatePublished - Jul 2010

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Molneuro
  • Proteins
  • Sysneuro

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