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Publication : The sodium-bicarbonate cotransporter Slc4a5 mediates feedback at the first synapse of vision.

First Author  Morikawa R Year  2024
Journal  Neuron Volume  112
Issue  22 Pages  3715-3733.e9
PubMed ID  39317184 Mgi Jnum  J:358138
Mgi Id  MGI:7779515 Doi  10.1016/j.neuron.2024.08.015
Citation  Morikawa R, et al. (2024) The sodium-bicarbonate cotransporter Slc4a5 mediates feedback at the first synapse of vision. Neuron
abstractText  Feedback at the photoreceptor synapse is the first neuronal circuit computation in vision, which influences downstream activity patterns within the visual system. Yet, the identity of the feedback signal and the mechanism of synaptic transmission are still not well understood. Here, we combined perturbations of cell-type-specific genes of mouse horizontal cells with two-photon imaging of the result of light-induced feedback in cones and showed that the electrogenic bicarbonate transporter Slc4a5, but not the electroneutral bicarbonate transporter Slc4a3, both expressed specifically in horizontal cells, is necessary for horizontal cell-to-cone feedback. Pharmacological blockage of bicarbonate transporters and buffering pH also abolished the feedback but blocking sodium-proton exchangers and GABA receptors did not. Our work suggests an unconventional mechanism of feedback at the first visual synapse: changes in horizontal cell voltage modulate bicarbonate transport to the cell, via Slc4a5, which leads to the modulation of feedback to cones.
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