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

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...

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Main Authors: Kochlamazashvili, Gaga (Author) , Henneberger, Christian (Author) , Bukalo, Olena (Author) , Dvoretskova, Elena (Author) , Senkov, Oleg (Author) , Lievens, Patricia M. -J. (Author) , Westenbroek, Ruth (Author) , Engel, Andreas K. (Author) , Catterall, William A. (Author) , Rusakov, Dmitri A. (Author) , Schachner, Melitta (Author) , Dityatev, Alexander (Author)
Format: Article (Journal)
Language:English
Published: July 14, 2010
In: Neuron
Year: 2010, Volume: 67, Issue: 1, Pages: 116-128
ISSN:1097-4199
DOI:10.1016/j.neuron.2010.05.030
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.neuron.2010.05.030
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0896627310004265
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Author Notes: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, and Alexander Dityatev
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Summary: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.
Item Description:In Titel erscheinen die Zeichen 2+ in der chemischen Formel hochgestellt
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Physical Description:Online Resource
ISSN:1097-4199
DOI:10.1016/j.neuron.2010.05.030

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