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eNeuro. 2016 Oct 21;3(5). pii: ENEURO.0130-16.2016. eCollection 2016 Sep-Oct.

Loss of SynDIG1 Reduces Excitatory Synapse Maturation But Not Formation In Vivo.

Author information

1
Department of Pharmacology, University of California, Davis, California 95616; Center for Neuroscience, University of California, Davis, California 95616.
2
Department of Pharmacology, University of California , Davis, California 95616.
3
Center for Neuroscience, University of California , Davis, California 95616.

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 strength in vitro. Here, we investigated the role of SynDIG1 in vivo in mice with a disruption of the SynDIG1 gene 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 the SynDIG1 promoter 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 in SynDIG1 mutant mice. Electrophysiological analyses show a decrease in AMPA and NMDA receptor function in SynDIG1-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 hippocampus in vivo.

KEYWORDS:

AMPA receptor; SynDIG1; excitatory synapse; hippocampus; synapse development; synapse maturation

PMID:
27800545
PMCID:
PMC5073248
DOI:
10.1523/ENEURO.0130-16.2016
[Indexed for MEDLINE]
Free PMC Article

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