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

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

Author information

1
Montréal Neurological Institute, Department of Neurology and Neurosurgery, 3801 Rue University, McGill University, Montréal, Québec H3A 2B4, Canada.
2
NSERC CREATE Neuroengineering Training Program, McGill University, Montréal, Québec H3A 2B4, Canada.
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Contributed equally

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.

PMID:
30770464
PMCID:
PMC6380201
[Available on 2020-03-01]
DOI:
10.1101/lm.049072.118

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