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Mrinalini Hoon, Rachel O Wong; Spatiotemporal order and interdependence of GABA receptor subtype expression in developing mouse retinal bipolar cells. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
Mouse retinal bipolar cells express distinct ionotropic GABA receptors on their axons and dendrites. ON bipolar cell axons predominantly express GABAAα1 and GABAC receptors and relatively low levels of GABAAα3 receptors, whereas their dendrites express only GABAAα1 receptors (Hoon et. al. 2015). The developmental sequence in the appearance of these bipolar cell GABA receptor subtypes is unknown. Further, it is not known if the developmental regulation of the expression of these receptor subtypes is interdependent. This study tested the hypothesis that the developmental expressions of different GABA receptor subtypes on mouse retinal bipolar cells are regulated separately.
We immunostained GABA receptor subtypes in retinas of transgenic mice with fluorescently labeled ON bipolar cells before and after eye-opening, which occurs at around postnatal day (P) 14. To determine if the expression patterns of GABA receptor subtypes are regulated separately, we used two GABAA receptor specific knockouts: The GABAAα3-subunit knockout (Yee et. al. 2005), and a line in which GABAAα1 subunit was conditionally knocked out in ON bipolar cells.
GABAAα3 receptors were present on bipolar cell axon terminals at P7 and subsequently downregulated as GABAAα1 receptor expression emerged around P9. GABAC receptors were expressed last, at around P12. ON bipolar cell dendrites never expressed GABAAα3 receptors, and GABAAα1 receptors appeared concurrently in the axon and dendrites. In the absence of GABAAα3 receptors, GABAAα1 receptors are much reduced in bipolar cell axons only. In contrast, the developmental profile of GABAAα3 receptors in bipolar cells is unchanged when GABAAα1 receptors are absent. Neither loss of GABAAα1 or GABAAα3 receptors affected GABAC receptor expression.
There is a temporal order in the emergence of various bipolar cell GABA receptor subtypes. Expression of GABAAα1 receptors on bipolar cell axons, but not on dendrites, requires preceding GABAAα3 expression. However, the developmental downregulation of GABAAα3 receptors in bipolar cells is not dependent on GABAAα1 upregulation. GABAC receptor expression in bipolar cell terminals is established independently of GABAA receptors.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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