Reelin signaling facilitates maturation of CA1 glutamatergic synapses.
Reelin signaling through the low-density lipoprotein receptor family members, apoliproprotein E receptor 2 (apoER2) and very-low-density lipoprotein receptor (VLDLR), plays a pivotal role in dictating neuronal lamination during embryonic brain development. Recent evidence suggests that this signaling system also plays a role in the postnatal brain to modulate synaptic transmission, plasticity, and cognitive behavior, mostly likely due to a functional coupling with N-methyl-d-aspartate (NMDA) receptors. In this study, we investigated the effects of reelin on the maturation of CA1 glutamatergic function using electrophysiological and biochemical approaches. In cultured hippocampal slices, reelin treatment increased the amplitude of AMPAR-mediated miniature excitatory postsynaptic currents and the evoked AMPA/NMDA receptor current ratios. In addition, reelin treatment also reduced the number of silent synapses, facilitated a developmental switch from NR2B to NR2A of NMDARs, and increased surface expression of AMPARs in CA1 tissue. In cultured hippocampal neurons from reeler embryos, reduced numbers of AMPAR subunit GluR1 and NMDAR subunit NR1 clustering were observed compared with those obtained from wild-type embryos. Supplementing reelin in the reeler culture obliterated these genotypic differences. These results demonstrate that reelin- and lipoprotein receptor-mediated signaling may operate during developmental maturation of hippocampal glutamatergic function and thus represent a potential important mechanism for controlling synaptic strength and plasticity in the postnatal hippocampus.
Qiu
Shenfeng
S
Department of Molecular Physiology and Biophysics, 754 Robinson Research Bldg., Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA.
Weeber
Edwin J
EJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014162:Transfection / Q000379:methods
D015816:Cell Adhesion Molecules, Neuronal; D018691:Excitatory Amino Acid Antagonists; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases