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

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

Author information

1
1] Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute (BSI), Wako-shi, Saitama 351-0198, Japan [2].
2
Education and Research Support Center, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
3
1] Laboratory for Neurobiology of Synapse, RIKEN BSI, Wako-shi, Saitama 351-0198, Japan [2] Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
4
1] Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute (BSI), Wako-shi, Saitama 351-0198, Japan [2] Department of Medical Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
5
Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute (BSI), Wako-shi, Saitama 351-0198, Japan.
6
Laboratory for Neurogenetics, RIKEN BSI, Wako-shi, Saitama 351-0198, Japan.
7
Laboratory for Molecular Psychiatry, RIKEN BSI, Wako-Shi, Saitama 351-0198, Japan.
8
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
9
National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka 420-8688, Japan.
10
Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki 036-8216, Japan.
11
Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
12
Support Unit for Animal Experiments, RIKEN BSI, Wako-shi, Saitama 351-0198, Japan.

Abstract

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.

PMID:
25047565
DOI:
10.1038/ncomms5501
[Indexed for MEDLINE]

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