The synaptic signaling scaffold GIT1 and attention deficit hyperactivity disorder

Eunjoon Kim
Eunjoon Kim
Department of Biological Sciences, Korea Aavanced Institite of Science and Technology, Korea
December 6, 2012, 16:40 ~ 17:20

Abstract :

Growing number of synaptic proteins are being associated with various brain diseases including schizophrenia, autism, and attention deficit hyperactivity disorder (ADHD). ADHD is a psychiatric disorder that affects ~5% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. We have identified a novel association between the synaptic protein GIT1 and ADHD. An intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility in humans. Git1- deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory. Hyperactivity in Git1−/− mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. In addition, amphetamine normalizes enhanced theta rhythms and impaired memory. GIT1 deficiency in mice leads to decreases in Rac1 signaling and inhibitory presynaptic input; furthermore, it shifts the neuronal excitation-inhibition balance in postsynaptic neurons toward excitation. Our study identifies a previously unknown involvement of GIT1 in human ADHD and shows that GIT1 deficiency in mice causes psychostimulant-responsive ADHD-like phenotypes. The Git1-deficient mice may represent a novel mouse model for ADHD and may be useful in studying ADHD mechanisms and for ADHD drug development.


Research Activities :

Synapse formation with various neuropsychiatric disorders including autism spectrum disorders, ADHD, schizophrenia, and intellectual disability.


Honors and Awards :

  • 2010: Member, Korean National Academy of Sciences Editorial board in eLife (a new open access journal, sponsored by HHMI, Wellcome Trust and the Max Planck Society), Experimental Neurobiology, Molecules and Cells, Neurosignals, Molecular Brain, Frontiers in Molecular Neuroscience
  • 2011: Best Research Award, KAIST
  • 2012: Selected as a director of new Institute for Basic Science (IBS) centers