dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients
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Date
2013
Authors
Manitt, C.
Eng, C.
Pokinko, M.
Ryan, R. T.
Torres-Berrio, A.
Lopez, J. P.
Yogendran, S. V.
Daubaras, M. J. J.
Grant, A.
Schmidt, E. R. E.
Journal Title
Journal ISSN
Volume Title
Publisher
Macmillan Publishers
Abstract
Adolescence 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.
Description
Sherpa Romeo green journal, open access
Keywords
Dopamine , Neurodevelopmental disorders , Neural circuit formation , Prefrontal cortex dysfunction , Resilience
Citation
Manitt, 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.2013.105