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bioRxiv · 10.1101/490680

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

Wong, E.·Glasgow, S. D.·Trigiani, L. J.·Chitsaz, D.·Rymar, V.·Sadikot, A.·Ruthazer, E. S.·Hamel, E.·Kennedy, T. E.
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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 post-natal 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 behaviour. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

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Wong, E., Glasgow, S. D., Trigiani, L. J., Chitsaz, D., Rymar, V., Sadikot, A., Ruthazer, E. S., Hamel, E., Kennedy, T. E.. 2018-12-08. Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.. https://doi.org/10.1101/490680

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