Article abstract


Nature Neuroscience 11, 667 - 675 (2008)
Published online: 27 April 2008 | doi:10.1038/nn.2117

Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration

Pamela S Lagali1,4, David Balya1,4, Gautam B Awatramani1,3,4, Thomas A Münch1, Douglas S Kim2, Volker Busskamp1, Constance L Cepko2 & Botond Roska1


Genetically encoded optical neuromodulators create an opportunity for circuit-specific intervention in neurological diseases. One of the diseases most amenable to this approach is retinal degeneration, where the loss of photoreceptors leads to complete blindness. To restore photosensitivity, we genetically targeted a light-activated cation channel, channelrhodopsin-2, to second-order neurons, ON bipolar cells, of degenerated retinas in vivo in the Pde6brd1 (also known as rd1) mouse model. In the absence of 'classical' photoreceptors, we found that ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells. The rescue of light sensitivity was selective to the ON circuits that would naturally respond to increases in brightness. Despite degeneration of the outer retina, our intervention restored transient responses and center-surround organization of ganglion cells. The resulting signals were relayed to the visual cortex and were sufficient for the animals to successfully perform optomotor behavioral tasks.

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  1. Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
  2. Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
  3. Present address: Department of Anatomy and Neurobiology, Dalhousie University, 5850 College Street, Halifax, NS B3H 1X5, Canada.
  4. These authors contributed equally to this work.

Correspondence to: Botond Roska1 e-mail: botond.roska@fmi.ch



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