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J Neurosci. 2013 Nov 6;33(45):17847-62. doi: 10.1523/JNEUROSCI.1373-13.2013.

Development and plasticity of outer retinal circuitry following genetic removal of horizontal cells.

Author information

1
Neuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, Center for Bio-Image Informatics, Department of Electrical and Computer Engineering, and Department of Psychological and Brain Sciences, University of California, Santa Barbara, California 93106, Department of Molecular Physiology and Biophysics and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, Department of Pediatrics, University of Texas Medical School, Houston, Texas 77030, Department of Medicine, Division of Neurology, Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina 27710, and Biological Imaging Core and Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.

Abstract

The present study examined the consequences of eliminating horizontal cells from the outer retina during embryogenesis upon the organization and assembly of the outer plexiform layer (OPL). Retinal horizontal cells exhibit a migration defect in Lim1-conditional knock-out (Lim1-CKO) mice and become mispositioned in the inner retina before birth, redirecting their dendrites into the inner plexiform layer. The resultant (mature) OPL, developing in the absence of horizontal cells, shows a retraction of rod spherules into the outer nuclear layer and a sprouting of rod bipolar cell dendrites to reach ectopic ribbon-protein puncta. Cone pedicles and the dendrites of type 7 cone bipolar cells retain their characteristic stratification and colocalization within the collapsed OPL, although both are atrophic and the spatial distribution of the pedicles is disrupted. Developmental analysis of Lim1-CKO retina reveals that components of the rod and cone pathways initially co-assemble within their normal strata in the OPL, indicating that horizontal cells are not required for the correct targeting of photoreceptor terminals or bipolar cell dendrites. As the rod spherules begin to retract during the second postnatal week, rod bipolar cells initially show no signs of ectopic growth, sprouting only subsequently and continuing to do so well after the eighth postnatal week. These results demonstrate the critical yet distinctive roles for horizontal cells on the rod and cone pathways and highlight a unique and as-yet-unrecognized maintenance function of an inhibitory interneuron that is not required for the initial targeting and co-stratification of other components in the circuit.

PMID:
24198374
PMCID:
PMC3818557
DOI:
10.1523/JNEUROSCI.1373-13.2013
[Indexed for MEDLINE]
Free PMC Article

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