TY - JOUR
T1 - The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca2+ 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
N1 - Funding Information:
We thank Fabio Morellini and Kristin Michael for helpful suggestions, Tommaso Fellin for FVB/N-Tg(GFAPGFP)14Mes/J mice, and Joerg Striessnig for the Ca v 1.3 expression vector. This work was supported by the Deutsche Forschungsgemeinschaft (DI 702/6-1 to A.D.), the Italian Institute of Technology (G.K., P.M.-J.L., and A.D.), the Wellcome Trust and Medical Research Council UK (D.A.R. and C.H.), and the New Jersey Commission for Spinal Cord Research (M.S). M.S. is a consultant at the Center for Neuroscience at Shantou University Medical College, China.
PY - 2010/7
Y1 - 2010/7
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 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.
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 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.
KW - Molneuro
KW - Proteins
KW - Sysneuro
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U2 - 10.1016/j.neuron.2010.05.030
DO - 10.1016/j.neuron.2010.05.030
M3 - Article
C2 - 20624596
AN - SCOPUS:77954475099
VL - 67
SP - 116
EP - 128
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -