Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures

Nat Commun. 2014 Jul 22;5:4501. doi: 10.1038/ncomms5501.


GABAergic interneurons are highly heterogeneous, and much is unknown about the specification and functional roles of their neural circuits. Here we show that a transinteraction of Elfn1 and mGluR7 controls targeted interneuron synapse development and that loss of Elfn1 results in hyperactivity and sensory-triggered epileptic seizures in mice. Elfn1 protein increases during postnatal development and localizes to postsynaptic sites of somatostatin-containing interneurons (SOM-INs) in the hippocampal CA1 stratum oriens and dentate gyrus (DG) hilus. Elfn1 knockout (KO) mice have deficits in mGluR7 recruitment to synaptic sites on SOM-INs, and presynaptic plasticity is impaired at these synapses. In patients with epilepsy and attention deficit hyperactivity disorder (ADHD), we find damaging missense mutations of ELFN1 that are clustered in the carboxy-terminal region required for mGluR7 recruitment. These results reveal a novel mechanism for interneuron subtype-specific neural circuit establishment and define a common basis bridging neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Animals
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Autistic Disorder / genetics
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Epilepsy / genetics*
  • Female
  • Humans
  • Interneurons / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / genetics
  • Polymorphism, Single Nucleotide
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / metabolism*
  • Seizures / genetics
  • Seizures / metabolism*
  • Young Adult


  • Elfn1 protein, human
  • Nerve Tissue Proteins
  • Receptors, Metabotropic Glutamate
  • extracellular leucine-rich repeat fibronectin containing 1 protein, mouse
  • metabotropic glutamate receptor 7