Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors

Neuron. 2014 Dec 3;84(5):1049-64. doi: 10.1016/j.neuron.2014.10.051. Epub 2014 Nov 20.

Abstract

The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial, largely due to the inherent difficulty recording neural activity in early development. Here, we describe genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a decoupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience.

Publication types

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

MeSH terms

  • Action Potentials / physiology*
  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Cyclic AMP / pharmacology
  • Cyclic GMP / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Functional Laterality
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Vitro Techniques
  • Meclofenamic Acid / pharmacology
  • Mice
  • Mice, Transgenic
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retina / cytology
  • Retina / physiology*
  • Retinal Ganglion Cells / physiology
  • Visual Pathways / growth & development*

Substances

  • Cyclooxygenase Inhibitors
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • RNA, Messenger
  • Receptors, Nicotinic
  • Repressor Proteins
  • nicotinic receptor beta2
  • Meclofenamic Acid
  • Cyclic AMP
  • Cyclic GMP
  • Calcium