The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels.
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The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels. / Kochlamazashvili, Gaga; Henneberger, Christian; Bukalo, Olena; Dvoretskova, Elena; Senkov, Oleg; Lievens, Patricia M-J; Westenbroek, Ruth; Engel, Andreas K.; Catterall, William A; Rusakov, Dmitri A; Schachner, Melitta; Dityatev, Alexander.
in: NEURON, Jahrgang 67, Nr. 1, 1, 2010, S. 116-128.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels.
AU - Kochlamazashvili, Gaga
AU - Henneberger, Christian
AU - Bukalo, Olena
AU - Dvoretskova, Elena
AU - Senkov, Oleg
AU - Lievens, Patricia M-J
AU - Westenbroek, Ruth
AU - Engel, Andreas K.
AU - Catterall, William A
AU - Rusakov, Dmitri A
AU - Schachner, Melitta
AU - Dityatev, Alexander
PY - 2010
Y1 - 2010
N2 - 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 Ca(2+) currents, decreased Ca(2+) transients mediated by L-type voltage-dependent Ca(2+) 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 Ca(v)1.2, but not Ca(v)1.3, 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 Ca(2+) channels.
AB - 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 Ca(2+) currents, decreased Ca(2+) transients mediated by L-type voltage-dependent Ca(2+) 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 Ca(v)1.2, but not Ca(v)1.3, 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 Ca(2+) channels.
M3 - SCORING: Zeitschriftenaufsatz
VL - 67
SP - 116
EP - 128
JO - NEURON
JF - NEURON
SN - 0896-6273
IS - 1
M1 - 1
ER -
