Feedback from horizontal cells to rod photoreceptors in vertebrate retina

J Neurosci. 2008 May 28;28(22):5691-5. doi: 10.1523/JNEUROSCI.0403-08.2008.


Retinal horizontal cells (HCs) provide negative feedback to cones, but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (I(Ca)) that do not always generate detectable depolarizing responses. We therefore recorded I(Ca) directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage-clamped HCs while simultaneously recording from rods in a salamander retinal slice preparation. Like HC feedback in cones, hyperpolarizing HCs from -14 to -54, -84, and -104 mV increased the amplitude of I(Ca) recorded from synaptically connected rods and caused hyperpolarizing shifts in I(Ca) voltage dependence. These effects were blocked by supplementing the bicarbonate-buffered saline solution with HEPES. In rods lacking light-responsive outer segments, hyperpolarizing neighboring HCs with light caused a negative activation shift and increased the amplitude of I(Ca). These changes in I(Ca) were blocked by HEPES and by inhibiting HC light responses with a glutamate antagonist, indicating that they were caused by HC feedback. These results show that rods, like cones, receive negative feedback from HCs that regulates the amplitude and voltage dependence of I(Ca). HC-to-rod feedback counters light-evoked decreases in synaptic output and thus shapes the transmission of rod responses to downstream visual neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Feedback / physiology*
  • HEPES / pharmacology
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Models, Neurological
  • Patch-Clamp Techniques
  • Photic Stimulation / methods
  • Retina / cytology*
  • Retinal Horizontal Cells / physiology*
  • Retinal Rod Photoreceptor Cells / physiology*
  • Urodela


  • Excitatory Amino Acid Antagonists
  • Kynurenic Acid