dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients

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dc.contributor.authorManitt, C.
dc.contributor.authorEng, C.
dc.contributor.authorPokinko, M.
dc.contributor.authorRyan, R. T.
dc.contributor.authorTorres-Berrio, A.
dc.contributor.authorLopez, J. P.
dc.contributor.authorYogendran, S. V.
dc.contributor.authorDaubaras, M. J. J.
dc.contributor.authorGrant, A.
dc.contributor.authorSchmidt, E. R. E.
dc.contributor.authorTronche, F.
dc.contributor.authorKrimpenfort, P.
dc.contributor.authorCooper, H. M.
dc.contributor.authorPasterkamp, R. J.
dc.contributor.authorKolb, Bryan
dc.contributor.authorTurecki, G.
dc.contributor.authorWong, T. P.
dc.contributor.authorNestler, E. J.
dc.contributor.authorGiros, B.
dc.contributor.authorFlores, C.
dc.date.accessioned2016-08-12T21:10:35Z
dc.date.available2016-08-12T21:10:35Z
dc.date.issued2013
dc.descriptionSherpa Romeo green journal, open accessen_US
dc.description.abstractAdolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationManitt, C., Eng, C., Pokinko, M., Ryan, M., Torres-Berrio, A., Lopez, J., ... Flores, C. (2013). dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients. Translational Psychiatry, 3, e338. doi:10.1038/tp.2013.105en_US
dc.identifier.urihttps://hdl.handle.net/10133/4576
dc.language.isoen_CAen_US
dc.publisherMacmillan Publishersen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionMcGill Universityen_US
dc.publisher.institutionUniversity Medical Center Utrechten_US
dc.publisher.institutionUniversite Pierre et Marie Curieen_US
dc.publisher.institutionThe Netherlands Cancer Instituteen_US
dc.publisher.institutionUniversity of Queenslanden_US
dc.publisher.institutionUniveristy of Lethbridgeen_US
dc.publisher.institutionMount Sinai School of Medicineen_US
dc.subjectDopamineen_US
dc.subjectNeurodevelopmental disordersen_US
dc.subjectNeural circuit formationen_US
dc.subjectPrefrontal cortex dysfunctionen_US
dc.subjectResilienceen_US
dc.titledcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patientsen_US
dc.typeArticleen_US
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