Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain
- Edwin W. Wong1,3,
- Stephen D. Glasgow1,2,3,
- Lianne J. Trigiani1,
- Daryan Chitsaz1,
- Vladimir Rymar1,
- Abbas Sadikot1,
- Edward S. Ruthazer1,
- Edith Hamel1 and
- Timothy E. Kennedy1,2
- 1Montréal Neurological Institute, Department of Neurology and Neurosurgery, 3801 Rue University, McGill University, Montréal, Québec H3A 2B4, Canada
- 2NSERC CREATE Neuroengineering Training Program, McGill University, Montréal, Québec H3A 2B4, Canada
- Corresponding author: timothy.kennedy{at}mcgill.ca
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↵3 These authors contributed equally to this work.
Abstract
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.
Footnotes
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.049072.118.
- Received December 8, 2018.
- Accepted January 18, 2019.
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