Retinal Input Directs the Recruitment of Inhibitory Interneurons Into Thalamic Visual Circuits

Neuron. 2014 Mar 5;81(5):1057-1069. doi: 10.1016/j.neuron.2014.01.032.

Abstract

Inhibitory interneurons (INs) critically control the excitability and plasticity of neuronal networks, but whether activity can direct INs into specific circuits during development is unknown. Here, we report that in the dorsal lateral geniculate nucleus (dLGN), which relays retinal input to the cortex, circuit activity is required for the migration, molecular differentiation, and functional integration of INs. We first characterize the prenatal origin and molecular identity of dLGN INs, revealing their recruitment from an Otx2(+) neuronal pool located in the adjacent ventral LGN. Using time-lapse and electrophysiological recordings, together with genetic and pharmacological perturbation of retinal waves, we show that retinal activity directs the navigation and circuit incorporation of dLGN INs during the first postnatal week, thereby regulating the inhibition of thalamocortical circuits. These findings identify an input-dependent mechanism regulating IN migration and circuit inhibition, which may account for the progressive recruitment of INs into expanding excitatory circuits during evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • Cell Movement / physiology*
  • Female
  • Fibroblast Growth Factor 8 / genetics
  • Fibroblast Growth Factor 8 / metabolism
  • GABAergic Neurons / cytology
  • GABAergic Neurons / physiology
  • Geniculate Bodies / cytology*
  • Geniculate Bodies / embryology
  • Geniculate Bodies / physiology
  • Green Fluorescent Proteins / genetics
  • Interneurons / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology
  • Otx Transcription Factors / genetics
  • Otx Transcription Factors / metabolism
  • Pregnancy
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism
  • Retina / cytology*
  • Retina / embryology
  • Retina / physiology
  • Synapses / physiology
  • Visual Pathways / cytology
  • Visual Pathways / embryology
  • Visual Pathways / physiology

Substances

  • Fgf8 protein, mouse
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • Receptors, Nicotinic
  • nicotinic receptor beta2
  • Green Fluorescent Proteins
  • Fibroblast Growth Factor 8