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J. Johnson, J.L. Duncan, H. Yang, R.T. Fremeau, Jr, R.H. Edwards, D.R. Copenhagen; Vesicular Glutamate Transporter 1 (VGLUT1) Is Required for Rod and Cone Mediated Signaling in the Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5337.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Glutamate is a major excitatory neurotransmitter in the CNS and retina. Vesicular glutamate transporters (VGLUTs) sequester glutamate into synaptic vesicles for exocytotic release. Previous studies have found that VGLUT1 is exclusively expressed in photoreceptor and bipolar terminals. We sought to determine the physiological role of VGLUT1 in transmitting rod and cone visually–evoked signals. Methods: We investigated the functional role of VGLUT1 using a knock out strategy. We used electroretinogram (ERG), flash Visual Evoked Potential (VEP) recordings, and pupil light response recordings to investigate synaptic transmission in the retina of VGLUT1 –/– mice. We also used immunohistochemistry and in situ hybridization. Results: No significant difference was found between the mean peak amplitude scotopic a–wave of VGLUT1 –/– mice and wild–type, suggesting that VGLUT1 –/– mice have normal photoreceptor signal transduction. However, VGLUT1 –/– mice have no discernable scotopic b–wave at all flash intensities, indicating the abolishment of signal transmission to rod bipolar cells. In addition, VGLUT1 –/– mice do not have a detectable photopic b–wave, indicating lack of transmission to cone–driven postsynaptic cells. VEP recordings found that visually–driven cortical activity was abolished in the VGLUT1 –/– mouse. These results indicate that VGLUT1–/– mice have no rod and cone mediated visual signaling. Interestingly, a pupil response is preserved in VGLUT1–/– mice, suggesting that the melanopsin mediated pupil response can be generated without VGLUT1 expression. We found that melanopsin ganglion cells express VGLUT2 consistent with the idea that VGLUT2 plays a major role in driving the pupil response. Conclusions: Abolishment of VGLUT1 results in the absence of rod and cone mediated visual signaling, and an absence of visually driven cortical activity. VGLUT1 –/– mice have a pupil light response, which is likely mediated by VGLUT2. We conclude that VGLUT1 has an essential role in the transmission of rod and cone evoked signals in the retina, while VGLUT2 likely has a role in the non–image forming response.
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