The scheduling of adolescence with Netrin-1 and UNC5C
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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 toward 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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Adolescence is evolutionarily conserved, with animal species also showing distinct markers of an adolescent state.
“it is increasingly recognized to be evolutionarily conserved, with animal species also showing distinct markers of an adolescent state [35–40].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [40]
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References 82 · Cited by 8
- Authors
- Hoops, D., Kyne, R., Salameh, S., MacGowan, D., Avramescu, R. G., Ewing, E., He, A. T., Orsini, T., Durand, A., Popescu, C., Zhao, J. M., Shatz, K., Li, L., Carroll, Q., Liu, G., Paul, M. J., & Flores, C.
- Affiliations
- Douglas Mental Health University Institute (CA)
- University at Buffalo, State University of New York (US)
- Department of Psychology, University at Buffalo
- University of Toledo (US)
- Corresponding author
- Flores, Cecilia
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2024-07-26
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC11281785
- OpenAlex
- W4378838611
- Cited by
- 8
- References
- 82
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Drug Abuse (R01DA037911)
- Canadian Institutes of Health Research (FRN: 156272, FRN: 170130)
- National Science and Engineering Research Council of Canada (RGPIN-2020-04703)
- National Science Foundation (IOS-1754878)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- adolescence, netrin-1, UNC5C, mesocortical dopamine pathway, prefrontal cortex, axon growth, seasonal photoperiod, Siberian hamster, sexual dimorphism, brain development, phase locking
- MeSH terms
- Netrin Receptors, Netrin-1, Animals, Axons, Female, Male, Phodopus, Prefrontal Cortex, Mice, Dopaminergic Neurons
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