Netrin-G1 regulates fear-like and anxiety-like behaviors in dissociable neural circuits

Sci Rep. 2016 Jun 27:6:28750. doi: 10.1038/srep28750.


In vertebrate mammals, distributed neural circuits in the brain are involved in emotion-related behavior. Netrin-G1 is a glycosyl-phosphatidylinositol-anchored synaptic adhesion molecule whose deficiency results in impaired fear-like and anxiety-like behaviors under specific circumstances. To understand the cell type and circuit specificity of these responses, we generated netrin-G1 conditional knockout mice with loss of expression in cortical excitatory neurons, inhibitory neurons, or thalamic neurons. Genetic deletion of netrin-G1 in cortical excitatory neurons resulted in altered anxiety-like behavior, but intact fear-like behavior, whereas loss of netrin-G1 in inhibitory neurons resulted in attenuated fear-like behavior, but intact anxiety-like behavior. These data indicate a remarkable double dissociation of fear-like and anxiety-like behaviors involving netrin-G1 in excitatory and inhibitory neurons, respectively. Our findings support a crucial role for netrin-G1 in dissociable neural circuits for the modulation of emotion-related behaviors, and provide genetic models for investigating the mechanisms underlying the dissociation. The results also suggest the involvement of glycosyl-phosphatidylinositol-anchored synaptic adhesion molecules in the development and pathogenesis of emotion-related behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics
  • Anxiety / metabolism*
  • Anxiety / pathology
  • Behavior, Animal*
  • Brain / metabolism*
  • Brain / pathology
  • Fear*
  • Mice
  • Nerve Net / metabolism*
  • Nerve Net / pathology
  • Netrins / genetics
  • Netrins / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology


  • Netrins
  • Ntng1 protein, mouse