Local Signals in Mouse Horizontal Cell Dendrites

Curr Biol. 2017 Dec 4;27(23):3603-3615.e5. doi: 10.1016/j.cub.2017.10.050. Epub 2017 Nov 22.


The mouse retina contains a single type of horizontal cell, a GABAergic interneuron that samples from all cone photoreceptors within reach and modulates their glutamatergic output via parallel feedback mechanisms. Because horizontal cells form an electrically coupled network, they have been implicated in global signal processing, such as large-scale contrast enhancement. Recently, it has been proposed that horizontal cells can also act locally at the level of individual cone photoreceptors. To test this possibility physiologically, we used two-photon microscopy to record light stimulus-evoked Ca2+ signals in cone axon terminals and horizontal cell dendrites as well as glutamate release in the outer plexiform layer. By selectively stimulating the two mouse cone opsins with green and UV light, we assessed whether signals from individual cones remain isolated within horizontal cell dendritic tips or whether they spread across the dendritic arbor. Consistent with the mouse's opsin expression gradient, we found that the Ca2+ signals recorded from dendrites of dorsal horizontal cells were dominated by M-opsin and those of ventral horizontal cells by S-opsin activation. The signals measured in neighboring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing. Rather, our experimental data and results from biophysically realistic modeling support the idea that horizontal cells can process cone input locally, extending the classical view of horizontal cell function. Pharmacologically removing horizontal cells from the circuitry reduced the sensitivity of the cone signal to low frequencies, suggesting that local horizontal cell feedback shapes the temporal properties of cone output.

Keywords: calcium; cone photoreceptor; dendrite; feedback; glutamate; horizontal cell; mouse; retina.

MeSH terms

  • Animals
  • Axons / physiology*
  • Calcium / metabolism
  • Dendrites / physiology*
  • Female
  • Glutamic Acid / metabolism
  • Male
  • Mice / physiology*
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • Retinal Cone Photoreceptor Cells / cytology
  • Retinal Cone Photoreceptor Cells / physiology*
  • Signal Transduction*


  • Glutamic Acid
  • Calcium