Injured adult retinal axons with Pten and Socs3 co-deletion reform active synapses with suprachiasmatic neurons

Neurobiol Dis. 2015 Jan:73:366-76. doi: 10.1016/j.nbd.2014.09.019. Epub 2014 Oct 16.

Abstract

Despite advances in promoting axonal regeneration after adult central nervous system injury, elicitation of a large number of lesion-passing axons reform active synaptic connections with natural target neurons remains limited. By deleting both Pten and Socs3 in retinal ganglion cells, we report that optic nerve axons after prechiasm lesion robustly reinnervate the hypothalamus, form new synapses with neurons in the suprachiasmatic nucleus (SCN), and re-integrate with the existing circuitry. Photic or electric stimulation of the retinal axons induces neuronal response in SCN. However both the innervation pattern and evoked responses are not completely restored by the regenerating axons, suggesting that combining with other strategies is necessary to overcome the defective rewiring. Our results support that boosting the intrinsic growth capacity in injured neurons promotes axonal reinnervation and rewiring.

Keywords: Axon regeneration and rewiring; Intrinsic mechanisms; Pre-chiasm lesion; Retinal ganglion cells; Suprachiasmatic nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology
  • Axons / physiology*
  • Hypothalamus / pathology
  • Hypothalamus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Regeneration / physiology*
  • Optic Nerve / pathology
  • Optic Nerve / physiology*
  • PTEN Phosphohydrolase* / genetics
  • Retinal Ganglion Cells / pathology
  • Retinal Ganglion Cells / physiology*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins* / genetics
  • Suprachiasmatic Nucleus / pathology
  • Suprachiasmatic Nucleus / physiology*
  • Synapses / pathology
  • Synapses / physiology*

Substances

  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • PTEN Phosphohydrolase
  • Pten protein, mouse