title: Loss of SynDIG1 Reduces Excitatory Synapse Maturation But Not FormationIn Vivo.
abstract: Modification of the strength of excitatory synaptic connections is a fundamental mechanism by which neural circuits are refined during development and learning. Synapse Differentiation Induced Gene 1 (SynDIG1) has been shown to play a key role in regulating synaptic strengthin vitro. Here, we investigated the role of SynDIG1in vivoin mice with a disruption of theSynDIG1gene rather than use an alternate loxP-flanked conditional mutant that we find retains a partial protein product. The gene-trap insertion with a reporter cassette mutant mice shows that theSynDIG1promoter is active during embryogenesis in the retina with some activity in the brain, and postnatally in the mouse hippocampus, cortex, hindbrain, and spinal cord. Ultrastructural analysis of the hippocampal CA1 region shows a decrease in the average PSD length of synapses and a decrease in the number of synapses with a mature phenotype. Intriguingly, the total synapse number appears to be increased inSynDIG1mutant mice. Electrophysiological analyses show a decrease in AMPA and NMDA receptor function inSynDIG1-deficient hippocampal neurons. Glutamate stimulation of individual dendritic spines in hippocampal slices from SynDIG1-deficient mice reveals increased short-term structural plasticity. Notably, the overall levels of PSD-95 or glutamate receptors enriched in postsynaptic biochemical fractions remain unaltered; however, activity-dependent synapse development is strongly compromised upon the loss of SynDIG1, supporting its importance for excitatory synapse maturation. Together, these data are consistent with a model in which SynDIG1 regulates the maturation of excitatory synapse structure and function in the mouse hippocampusin vivo.
authors: Department of Pharmacology, University of California, Davis, California 95616; Center for Neuroscience, University of California, Davis, California 95616.
authors: George
authors: 0000-0003-2186-1179
authors: G
authors: Chenaux
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: Lucas
authors: 0000-0003-3235-5140
authors: L
authors: Matt
authors: Center for Neuroscience, University of California , Davis, California 95616.
authors: Travis C
authors: 0000-0002-7995-9315
authors: TC
authors: Hill
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: Inderpreet
authors: I
authors: Kaur
authors: Center for Neuroscience, University of California , Davis, California 95616.
authors: Xiao-Bo
authors: XB
authors: Liu
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: Lyndsey M
authors: LM
authors: Kirk
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: David J
authors: DJ
authors: Speca
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: Samuel A
authors: SA
authors: McMahon
authors: Center for Neuroscience, University of California , Davis, California 95616.
authors: Karen
authors: K
authors: Zito
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: Johannes W
authors: 0000-0001-7960-7531
authors: JW
authors: Hell
authors: Department of Pharmacology, University of California , Davis, California 95616.
authors: Elva
authors: 0000-0002-3287-7515
authors: E
authors: Díaz
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D046509:Tissue Culture Techniques
chemical_list: D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C000624309:SynDIG1 protein, mouse; D018698:Glutamic Acid; D051528:Guanylate Kinases
keywords: AMPA receptor; SynDIG1; excitatory synapse; hippocampus; synapse development; synapse maturation