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The Nogo Receptor Ligand LGI1 Regulates Synapse Number and Synaptic Activity in Hippocampal and Cortical Neurons.

eNeuro | 2018

Leucine-rich glioma-inactivated protein 1 (LGI1) is a secreted neuronal protein and a Nogo receptor 1 (NgR1) ligand. Mutations in LGI1 in humans causes autosomal dominant lateral temporal lobe epilepsy and homozygous deletion of LGI1 in mice results in severe epileptic seizures that cause early postnatal death. NgR1 plays an important role in the development of CNS synapses and circuitry by limiting plasticity in the adult cortex via the activation of RhoA. These relationships and functions prompted us to examine the effect of LGI1 on synapse formation in vitro and in vivo. We report that application of LGI1 increases synaptic density in neuronal culture and that LGI1 null hippocampus has fewer dendritic mushroom spines than in wild-type (WT) littermates. Further, our electrophysiological investigations demonstrate that LGI1 null hippocampal neurons possess fewer and weaker synapses. RhoA activity is significantly increased in cortical cultures derived from LGI1 null mice and using a reconstituted system; we show directly that LGI1 antagonizes NgR1-tumor necrosis factor receptor orphan Y (TROY) signaling. Our data suggests that LGI1 enhances synapse formation in cortical and hippocampal neurons by reducing NgR1 signaling.

Pubmed ID: 30225353 RIS Download

Additional research tools detected in this publication

Associated grants

  • Agency: CIHR, Canada
    Id: 37850
  • Agency: CIHR, Canada
    Id: 130239

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This is a list of tools and resources that we have found mentioned in this publication.


ImageJ (tool)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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Covance (tool)

RRID:SCR_001224

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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LGI1 (C-19) (antibody)

RRID:AB_2134990

This polyclonal targets LGI1

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Neuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (antibody)

RRID:AB_2313773

This monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified

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Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Zeiss Axioskop Software (software resource)

RRID:SCR_014587

THIS RESOURCE IS NO LONGER IN SERVCE, documented January 19, 2022. Software used to control the Zeiss Axioskop microscope.

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COS-7 (cell line)

RRID:CVCL_0224

Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Neuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (antibody)

RRID:AB_2313773

This monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

Zeiss Axioskop Software (software resource)

RRID:SCR_014587

THIS RESOURCE IS NO LONGER IN SERVCE, documented January 19, 2022. Software used to control the Zeiss Axioskop microscope.

View all literature mentions

COS-7 (cell line)

RRID:CVCL_0224

Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

View all literature mentions

C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

LGI1 (C-19) (antibody)

RRID:AB_2134990

This polyclonal targets LGI1

View all literature mentions

Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions

LGI1 (C-19) (antibody)

RRID:AB_2134990

This polyclonal targets LGI1

View all literature mentions

Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions