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

Curr Opin Neurobiol. 2018 Feb:48:17-29. doi: 10.1016/j.conb.2017.08.003. Epub 2017 Aug 30.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Dopamine / metabolism*
  • Humans
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neurodevelopmental Disorders* / metabolism
  • Neurodevelopmental Disorders* / pathology
  • Neurodevelopmental Disorders* / physiopathology
  • Research Design / trends
  • Research* / instrumentation
  • Research* / trends

Substances

  • Dopamine