Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells

J Physiol. 2014 Apr 1;592(7):1619-36. doi: 10.1113/jphysiol.2013.262782. Epub 2014 Jan 6.


Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non-image-forming visual responses, including pupillary constriction, circadian photoentrainment and suppression of pineal melatonin secretion. Five morphological types of ipRGCs, M1-M5, have been identified in mice. In order to understand their functions better, we studied the photoresponses of all five cell types, by whole-cell recording from fluorescently labelled ipRGCs visualized using multiphoton microscopy. All ipRGC types generated melanopsin-based ('intrinsic') as well as synaptically driven ('extrinsic') light responses. The intrinsic photoresponses of M1 cells were lower threshold, higher amplitude and faster than those of M2-M5. The peak amplitudes of extrinsic light responses differed among the ipRGC types; however, the responses of all cell types had comparable thresholds, kinetics and waveforms, and all cells received rod input. While all five types exhibited inhibitory amacrine-cell and excitatory bipolar-cell inputs from the 'on' channel, M1 and M3 received additional 'off'-channel inhibition, possibly through their 'off'-sublamina dendrites. The M2-M5 ipRGCs had centre-surround-organized receptive fields, implicating a capacity to detect spatial contrast. In contrast, the receptive fields of M1 cells lacked surround antagonism, which might be caused by the surround of the inhibitory input nullifying the surround of the excitatory input. All ipRGCs responded robustly to a wide range of motion speeds, and M1-M4 cells appeared tuned to different speeds, suggesting that they might analyse the speed of motion. Retrograde labelling revealed that M1-M4 cells project to the superior colliculus, suggesting that the contrast and motion information signalled by these cells could be used by this sensorimotor area to detect novel objects and motion in the visual field.

Publication types

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

MeSH terms

  • Animals
  • Contrast Sensitivity / radiation effects
  • Evoked Potentials
  • Female
  • GTP-Binding Protein alpha Subunits / deficiency
  • GTP-Binding Protein alpha Subunits / genetics
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / deficiency
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Kinetics
  • Light Signal Transduction / radiation effects*
  • Light*
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence, Multiphoton
  • Motion Perception / radiation effects
  • Pattern Recognition, Visual / radiation effects
  • Photic Stimulation
  • Retinal Ganglion Cells / classification
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / radiation effects*
  • Space Perception / radiation effects
  • Superior Colliculi / metabolism
  • Superior Colliculi / radiation effects
  • Transducin / deficiency
  • Transducin / genetics
  • Vision, Ocular / radiation effects
  • Visual Fields / radiation effects
  • Visual Pathways / metabolism
  • Visual Pathways / radiation effects
  • Visual Perception / radiation effects*


  • GTP-Binding Protein alpha Subunits
  • Gnat1 protein, mouse
  • Gnat2 protein, mouse
  • Green Fluorescent Proteins
  • Heterotrimeric GTP-Binding Proteins
  • Transducin