Neuronal Ig/Caspr recognition promotes the formation of axoaxonic synapses in mouse spinal cord

Neuron. 2014 Jan 8;81(1):120-9. doi: 10.1016/j.neuron.2013.10.060.

Abstract

Inhibitory microcircuits are wired with a precision that underlies their complex regulatory roles in neural information processing. In the spinal cord, one specialized class of GABAergic interneurons (GABApre) mediates presynaptic inhibitory control of sensory-motor synapses. The synaptic targeting of these GABAergic neurons exhibits an absolute dependence on proprioceptive sensory terminals, yet the molecular underpinnings of this specialized axoaxonic organization remain unclear. Here, we show that sensory expression of an NB2 (Contactin5)/Caspr4 coreceptor complex, together with spinal interneuron expression of NrCAM/CHL1, directs the high-density accumulation of GABAergic boutons on sensory terminals. Moreover, genetic elimination of NB2 results in a disproportionate stripping of inhibitory boutons from high-density GABApre-sensory synapses, suggesting that the preterminal axons of GABApre neurons compete for access to individual sensory terminals. Our findings define a recognition complex that contributes to the assembly and organization of a specialized GABAergic microcircuit.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Axons / physiology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Computational Biology
  • Flow Cytometry
  • Gene Expression Regulation, Developmental / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Mutation / genetics
  • Parvalbumins / genetics
  • Parvalbumins / metabolism
  • Presynaptic Terminals / physiology*
  • Sensory Receptor Cells / classification
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / metabolism
  • Spinal Cord / cytology*
  • Synapses / physiology*
  • Transcription Factors / metabolism

Substances

  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Cntnap1 protein, mouse
  • Kirrel3 protein, mouse
  • Luminescent Proteins
  • Membrane Proteins
  • NB-2 protein, mouse
  • Parvalbumins
  • Transcription Factors
  • transcription factor PTF1