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Updated: Jun 12, 2025

Multi-photon Intracellular Sodium Imaging Combined with UV-mediated Focal Uncaging of Glutamate in CA1 Pyramidal Neurons
Published on: October 8, 2014
The sodium-bicarbonate cotransporter Slc4a5 mediates feedback at the first synapse of vision
Rei Morikawa1, Tiago M Rodrigues2, Helene Marianne Schreyer1
1Institute of Molecular and Clinical Ophthalmology Basel, 4031 Basel, Switzerland.
Abstract:
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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