Format

Send to

Choose Destination
Neuron. 2016 Jan 6;89(1):177-93. doi: 10.1016/j.neuron.2015.11.032. Epub 2015 Dec 17.

Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity.

Author information

1
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
2
Bio Engineering Laboratory, Department of Biosystems Science and Engineering of ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
3
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
4
Department of Ophthalmology, Semmelweis University, Mária u. 39, 1085 Budapest, Hungary.
5
Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Tűzoltó u. 58, 1094 Budapest, Hungary.
6
Laboratory and Animal Services, Novartis Institute for Biomedical Research, Fabrikstrasse 28, 4056 Basel, Switzerland.
7
Jules-Gonin Eye Hospital, Avenue de France 15, 1000 Lausanne, Switzerland.
8
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Department of Ophthalmology, University of Basel, Mittlere Strasse 91, 4031 Basel, Switzerland. Electronic address: botond.roska@fmi.ch.

Abstract

Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.

PMID:
26711119
PMCID:
PMC4712192
DOI:
10.1016/j.neuron.2015.11.032
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center