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M. Haug, Y.-Y. Huang, M. Gesemann, S. C. F. Neuhauss; Expression and Function of mGluR6 in the Zebrafish Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4137.
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Metabotropic glutamate receptors (mGluRs) have been identified at all synapses of the vertebrate retina, where they likely regulate neurotransmitter release. The only example of an mGluR functioning in direct synaptic transmission is mGluR6, which is expressed on ON-bipolar cell dendrites and is found to mediate the ON-response in the mammalian retina. However, data from lower vertebrates propose a division of labor of the ON-bipolar cell response. mGluR6 is suggested to be only responsible for the scotopic ON-response, whereas most likely a glutamate transporter fulfills a similar function in photopic vision. We use the cone dominant retina of zebrafish to assess this hypothesis and to define the functional role of mGluR6 in teleost vision.
Expression of mGluR6 in larval zebrafish retina was assessed by RNA in situ hybridization and immunohistochemistry. To functionally analyze mGluR6 paralogs, ERG and OKR measurements are currently performed on morpholino antisense injected larvae.
Phylogenetic analysis of mGluR6 reveals the occurrence of two zebrafish mGluR6 paralogs, mGluR6a and -6b. The RNA of both paralogs is expressed in retinal ganglion cells of 5 day old fish, whereas the proteins are additionally detected in the IPL, INL and OPL, suggesting a higher sensitivity of immunohistochemistry. Preliminary data show that diminishing the mGluR6b protein level results in a decreased ERG b-wave but has, if any, only a slight effect on the optokinetic response. Depletion of mGluR6a is in progress.
In contrast to mammals, where mGluR6 is expressed in ON-bipolar cells, we locate both genes predominantly in retinal ganglion cells by in situ hybridization. This localization is confirmed by immunohistochemical analysis, however, we additionally detect both mGluR6 proteins in other layers of the inner retina and in the OPL. Behavioral analysis of mGluR6b deficient larvae provides evidence that this protein plays a role in the cone ON-bipolar cell pathway. Future work will include the depletion of mGluR6a to unravel its function in the teleost retina.
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