Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain

Learn Mem. 2019 Feb 15;26(3):77-83. doi: 10.1101/lm.049072.118. Print 2019 Mar.


Netrin-1 was initially characterized as an axon guidance molecule that is essential for normal embryonic neural development; however, many types of neurons continue to express netrin-1 in the postnatal and adult mammalian brain. Netrin-1 and the netrin receptor DCC are both enriched at synapses. In the adult hippocampus, activity-dependent secretion of netrin-1 by neurons potentiates glutamatergic synapse function, and is critical for long-term potentiation, an experimental cellular model of learning and memory. Here, we assessed the impact of neuronal expression of netrin-1 in the adult brain on behavior using tests of learning and memory. We show that adult mice exhibit impaired spatial memory following conditional deletion of netrin-1 from glutamatergic neurons in the hippocampus and neocortex. Further, we provide evidence that mice with conditional deletion of netrin-1 do not display aberrant anxiety-like phenotypes and show a reduction in self-grooming behavior. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Female
  • Glutamic Acid / physiology
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neocortex / metabolism
  • Neocortex / physiology*
  • Netrin-1 / metabolism
  • Netrin-1 / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Spatial Memory / physiology*


  • Ntn1 protein, mouse
  • Netrin-1
  • Glutamic Acid

Grant support