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E. D. Eggers, P. D. Lukasiewicz; Distinct Regulation of Local and Lateral Bipolar Cell Presynaptic Inhibition. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4905.
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© ARVO (1962-2015); The Authors (2016-present)
Inner retinal inhibition modulates the timing of bipolar cell signaling and plays a significant role in determining receptive field surrounds. Bipolar cells receive two types of IPL inhibition - local inhibition from feedback amacrine cell connections, and lateral inhibition from more distant amacrine cells. We previously showed that lateral inhibition evoked by full-field light stimuli is regulated by serial connections between amacrine cells mediated by GABAA receptors. Here, we investigated whether these serial connections differentially regulate lateral and feedback inhibition.
Light-evoked inhibitory postsynaptic currents (L-IPSCs) were recorded from dark-adapted bipolar cells in mouse retinal slices in the whole-cell voltage clamp configuration. Light responses were generated by full-field illumination with an LED or DLP-generated stimuli of varying sizes, projected through the microscope objective. Feedback (f)IPSCs were recorded from light-adapted bipolar cells that were depolarized from -60 to 0 mV for 500 ms. L-IPSCs and fIPSCs were isolated by recording at the reversal potential for cation-mediated currents. Receptor-specific inputs were isolated using bicuculline, TPMPA and strychnine. Sulfarhodamine was included in the pipettes to identify morphological bipolar cell types.
Blocking serial connections between amacrine cells with a GABAA receptor antagonist increased bipolar cell GABAergic L-IPSCs. However, depolarization-induced fIPSCs in bipolar cells, mediated by GABA, were decreased by antagonizing GABAA receptors, suggesting that serial connections do not modulate fIPSCs. We then tested whether local vs. lateral L-IPSCs were differentially modulated by serial inhibition. We found that local L-IPSCs evoked by narrow field light stimuli were decreased by blocking GABAA receptors, suggesting that serial connections do not modulate this local inhibition. Conversely, L-IPSCs evoked by wide field stimuli were significantly increased by blocking GABAA receptors, suggesting that these responses are normally inhibited by serial connections.
We found two distinct forms of inhibition of bipolar cells, local and lateral, that were differentially modulated by GABAA receptor mediated serial connections. Local inhibition was not affected by serial inhibition, potentially preserving the temporal fidelity of narrow-field light responses. In contrast lateral inhibition was limited by serial inhibition, potentially regulating the spatial receptive fields of bipolar cells.
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