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Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina
09:05

Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina

Published on: May 6, 2015

Proton-mediated feedback inhibition of presynaptic calcium channels at the cone photoreceptor synapse

John P Vessey1, Anna K Stratis, Bryan A Daniels

  • 1Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 22, 2005
PubMed

Insights

Horizontal cells regulate synaptic cleft pH to mediate inhibitory feedback to cone photoreceptors, influencing visual processing in the retina. This pH signaling impacts visual perception and retinal circuit function.

Area of Science:

  • Neuroscience
  • Retinal Physiology
  • Cellular Signaling

Background:

  • Center-surround antagonistic receptive fields are crucial for visual processing.
  • Inhibitory feedback from horizontal cells (HCs) to cone photoreceptors modulates presynaptic calcium channels, but the signaling mechanism is unknown.
  • Proposed mechanisms include neurotransmitters and ephaptic effects.

Purpose of the Study:

  • To investigate if proton concentration (pH) in the synaptic cleft mediates feedback from HCs to cones.
  • To elucidate the role of HCs in regulating synaptic cleft pH.

Main Methods:

  • Assessed feedback in goldfish retinal explants by measuring HC responses to light and the effects of pH buffering.
  • Used Fluo-4 imaging in zebrafish retinal slices to measure cone calcium signals.
  • Applied pharmacological agents (K+, kainic acid, CNQX) and manipulated extracellular pH to probe HC-cone interactions.
  • Performed voltage clamp on isolated HCs to identify ion conductances.

Main Results:

  • Strengthened pH buffering reduced HC rollback and cone depolarization to red light.
  • Depolarizing HCs (kainic acid) decreased cone calcium signals, while hyperpolarizing HCs (CNQX) increased them, indicating altered feedback.
  • Feedback signals were blocked by elevated pH buffering, amiloride, and divalent cations.
  • Isolated HCs exhibited an amiloride-sensitive conductance potentially regulating cleft pH.

Conclusions:

  • Horizontal cells regulate synaptic cleft pH, which acts as the feedback signal to cone photoreceptors.
  • This pH-mediated feedback modulates presynaptic calcium influx in cones.
  • The findings reveal a novel mechanism for visual information processing in the outer retina.

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