Circuit Reorganization Shapes the Developing Human Foveal Midget Connectome toward Single-Cone Resolution

Neuron. 2020 Dec 9;108(5):905-918.e3. doi: 10.1016/j.neuron.2020.09.014. Epub 2020 Oct 6.


The human visual pathway is specialized for the perception of fine spatial detail. The neural circuitry that determines visual acuity begins in the retinal fovea, where the resolution afforded by a dense array of cone photoreceptors is preserved in the retinal output by a remarkable non-divergent circuit: cone → midget bipolar interneuron → midget ganglion cell (the "private line"). How the private line develops is unknown; it could involve early specification of extremely precise synaptic connections or, by contrast, emerge slowly in concordance with the gradual maturation of foveal architecture and visual sensitivity. To distinguish between these hypotheses, we reconstructed the midget circuitry in the fetal human fovea by serial electron microscopy. We discovered that the midget private line is sculpted by synaptic remodeling beginning early in fetal life, with midget bipolar cells contacting a single cone by mid-gestation and bipolar cell-ganglion cell connectivity undergoing a more protracted period of refinement.

Keywords: circuit development; high-acuity vision; human fovea; midget bipolar cell; midget ganglion cell; retinal development; synaptic refinement.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Connectome / methods*
  • Female
  • Fetus
  • Fovea Centralis / diagnostic imaging*
  • Fovea Centralis / growth & development
  • Fovea Centralis / ultrastructure*
  • Humans
  • Imaging, Three-Dimensional / methods
  • Male
  • Nerve Net / diagnostic imaging
  • Nerve Net / growth & development*
  • Nerve Net / ultrastructure*
  • Retinal Cone Photoreceptor Cells / physiology
  • Retinal Cone Photoreceptor Cells / ultrastructure*
  • Visual Pathways / diagnostic imaging
  • Visual Pathways / growth & development
  • Visual Pathways / ultrastructure
  • Young Adult