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Published February 2018 | Accepted Version
Journal Article Open

Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research


Neurodevelopmental disorders (NDDs) represent a diverse group of syndromes characterized by abnormal development of the central nervous system and whose symptomatology includes cognitive, emotional, sensory, and motor impairments. The identification of causative genetic defects has allowed for creation of transgenic NDD mouse models that have revealed pathophysiological mechanisms of disease phenotypes in a neural circuit- and cell type-specific manner. Mouse models of several syndromes, including Rett syndrome, Fragile X syndrome, Angelman syndrome, Neurofibromatosis type 1, etc., exhibit abnormalities in the structure and function of dopaminergic circuitry, which regulates motivation, motor behavior, sociability, attention, and executive function. Recent advances in technologies for functional circuit mapping, including tissue clearing, viral vector-based tracing methods, and optical readouts of neural activity, have refined our knowledge of dopaminergic circuits in unperturbed states, yet these tools have not been widely applied to NDD research. Here, we will review recent findings exploring dopaminergic function in NDD models and discuss the promise of new tools to probe NDD pathophysiology in these circuits.

Additional Information

© 2017 Elsevier Ltd. Available online 30 August 2017. This review comes from a themed issue on Neurobiology of disease Edited by Anatol Kreitzer and Claudia Bagni. We would like to acknowledge support from the Children's Tumor Foundation (Young Investigator Award 2016-01-006 to JER), the National Institutes of Health (IDP20D017782 and R01AG047664 to VG), the Heritage Medical Research Institute (VG), and the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. We would like to thank Jennifer Treweek, Benjamin Deverman, Ken Chan, Min Jang, Alon Greenbaum, and Ryan Cho for histological images used in the manuscript figures. Conflict of interest statement: Nothing declared.

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