The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels.

Kochlamazashvili, G; Henneberger, C; Bukalo, O; Dvoretskova, E; Senkov, O; Lievens, Patricia; Westenbroek, R; Engel, Ak; Catterall, Wa; Rusakov, Da; Schachner, M; Dityatev, A.

doi:10.1016/j.neuron.2010.05.030

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 medi- ated by L-type voltage-dependent Ca2+ channels (L-VDCCs) in postsynaptic dendritic shafts and spines, and abolished an L-VDCC-dependent compo- nent 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 hyal- uronidase impaired contextual fear conditioning. Our observations unveil a previously unrecognized mech- anism by which the perisynaptic extracellular matrix influences use-dependent synaptic plasticity through regulation of dendritic Ca2+ channels.

Titolo:	The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels.
Autori:	Kochlamazashvili G Henneberger C Bukalo O Dvoretskova E Senkov O LIEVENS, Patricia Westenbroek R Engel AK Catterall WA Rusakov DA Schachner M Dityatev A. mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2010
Rivista:	NEURON
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 medi- ated by L-type voltage-dependent Ca2+ channels (L-VDCCs) in postsynaptic dendritic shafts and spines, and abolished an L-VDCC-dependent compo- nent 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 hyal- uronidase impaired contextual fear conditioning. Our observations unveil a previously unrecognized mech- anism by which the perisynaptic extracellular matrix influences use-dependent synaptic plasticity through regulation of dendritic Ca2+ channels.
Handle:	http://hdl.handle.net/11562/581550
Appare nelle tipologie:	01.01 Articolo in Rivista

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