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

• Published in: Neuron (Cambridge, Mass.) Mass.), 2016-01, Vol.89 (1), p.177-193
• Main Authors: Yonehara, Keisuke, Fiscella, Michele, Drinnenberg, Antonia, Esposti, Federico, Trenholm, Stuart, Krol, Jacek, Franke, Felix, Scherf, Brigitte Gross, Kusnyerik, Akos, Müller, Jan, Szabo, Arnold, Jüttner, Josephine, Cordoba, Francisco, Reddy, Ashrithpal Police, Németh, János, Nagy, Zoltán Zsolt, Munier, Francis, Hierlemann, Andreas, Roska, Botond
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Amacrine Cells - cytology; Animals; Behavior; Councils; Cytoskeletal Proteins - metabolism; Experiments; Eye movements; Genetic engineering; Mice, Transgenic; Motion Perception - physiology; Nerve Net - physiology; Neural Inhibition - physiology; Neurons; Nystagmus, Congenital - metabolism; Photic Stimulation - methods; Retina - physiology; Retinal Ganglion Cells - cytology; Synapses - metabolism; Visual Pathways - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.11.032

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. [Display omitted] •FRMD7 is required for the horizontal optokinetic reflex in mice as in humans•Horizontal direction selectivity is lost in the retina of FRMD7 mutant mice•Asymmetry of inhibitory inputs to horizontal DS cells is lost in FRMD7 mutant mice•FRMD7 is expressed in ChAT-expressing cells in the retina of mice and primates Yonehara et al. show that FRMD7, a gene that is defective in human congenital nystagmus, is required in the mouse retina to establish spatially asymmetric inhibitory inputs from starburst cells to horizontal direction-selective ganglion cells.