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R.C. Renteria, S. Nakanishi, D.R. Copenhagen; Retinal ON Pathways Suppress OFF Pathway Responses by at Least Two, Separate Neuronal Circuits . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2275.
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Purpose: We sought to determine the synaptic circuits by which signals in ON pathways suppress light–evoked signals in OFF pathways. Light–evoked ON responses are known to inhibit OFF pathways. Light responses recorded in mGluR6 –/– mouse retina revealed the properties of OFF responses in the absence of ON signals. We used pharmacological manipulations in wild type (WT) mice to dissect response suppression by the ON pathways. Methods: Light–evoked spiking responses of retinal ganglion cells (RGCs) were recorded extracellularly from mGluR6 –/– and WT retinas in the presence of antagonists to GABA and glycine receptors and in APB, an mGluR6 agonist that abolishes visual signals in ON bipolar cells. Results: A greater percentage of RGCs recorded from mGluR6 –/– retinas have robust OFF responses compared to WT responses. In addition, a large percentage of mGluR6–/– RGCs have a long latency ON response to sustained light stimuli. Both of these responses appear to be mediated by the OFF pathway. In the WT retina, APB (100 µM) had mixed effects on OFF responses, but it unmasked a long latency ON response in a majority of RGCs. A cocktail of GABA and glycine receptor antagonists augmented OFF responses in many neurons, revealed OFF responses in some neurons that previously only responded to light onset, and unmasked long latency ON responses in many RGCs. Subsequent application of APB in the presence of the inhibitory antagonists caused additional RGCs to respond with a long latency ON response and OFF responses of some RGCs to increase even further. Conclusions: These results are consistent with ON signals acting to suppress RGCs that have OFF responses both by a direct, APB–sensitive, glutamatergic action and also by activation of inhibitory neuronal circuitry. In addition, these results suggest that long latency responses during a light step can be generated in the OFF pathways.
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