The scheduling of adolescence with Netrin-1 and UNC5C

Hoops, D.; Kyne, R. F.; Salameh, S.; Ewing, E.; He, A. T.; Orsini, T.; Durand, A.; Popescu, C.; Zhao, J. M.; Schatz, K. C.; Lin, L.; Carroll, Q. E.; Liu, G.; Paul, M. J.; Flores, C.

doi:10.1101/2023.01.19.521267

bioRxiv · 10.1101/2023.01.19.521267

The scheduling of adolescence with Netrin-1 and UNC5C

Hoops, D.·Kyne, R. F.·Salameh, S.·Ewing, E.·He, A. T.·Orsini, T.·Durand, A.·Popescu, C.·Zhao, J. M.·Schatz, K. C.·Lin, L.·Carroll, Q. E.·Liu, G.·Paul, M. J.·Flores, C.

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Abstract

Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells - disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner - delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

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Hoops, D., Kyne, R. F., Salameh, S., Ewing, E., He, A. T., Orsini, T., Durand, A., Popescu, C., Zhao, J. M., Schatz, K. C., Lin, L., Carroll, Q. E., Liu, G., Paul, M. J., Flores, C.. 2023-01-20. The scheduling of adolescence with Netrin-1 and UNC5C. https://doi.org/10.1101/2023.01.19.521267

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