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

Wong, Edwin W., Glasgow, Stephen D., Trigiani, Lianne J., Chitsaz, Daryan, Rymar, Vladimir, Sadikot, Abbas, Ruthazer, Edward S., Hamel, Edith, Kennedy, Timothy E.·2019·Learning & Memory
DOI 10.1101/lm.049072.118PMC PMC6380201

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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.

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Metadata

Authors
Wong, E. W., Glasgow, S. D., Trigiani, L. J., Chitsaz, D., Rymar, V., Sadikot, A., Ruthazer, E. S., Hamel, E., & Kennedy, T. E.
ORCID
Venue
Learning & Memory
Publisher
Cold Spring Harbor Laboratory
Published
2019-02-15
Volume
26
Issue
3
Pages
77-83
ISSN
1549-5485
DOI
10.1101/lm.049072.118
PMC
PMC6380201
Cited by
30
References
9
Language
en
Funders
  • Healthy Brains for Healthy Lives
  • Fonds de la Recherche Québec – Santé
  • Canadian Institute for Health Research
  • CIHR
  • Alzheimer Society of Canada
  • Canadian Vascular Network
  • HBHL

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