Dysfunction of the corticostriatal pathway in autism spectrum disorders

J Neurosci Res. 2020 Nov;98(11):2130-2147. doi: 10.1002/jnr.24560. Epub 2019 Nov 22.


The corticostriatal pathway that carries sensory, motor, and limbic information to the striatum plays a critical role in motor control, action selection, and reward. Dysfunction of this pathway is associated with many neurological and psychiatric disorders. Corticostriatal synapses have unique features in their cortical origins and striatal targets. In this review, we first describe axonal growth and synaptogenesis in the corticostriatal pathway during development, and then summarize the current understanding of the molecular bases of synaptic transmission and plasticity at mature corticostriatal synapses. Genes associated with autism spectrum disorder (ASD) have been implicated in axonal growth abnormalities, imbalance of the synaptic excitation/inhibition ratio, and altered long-term synaptic plasticity in the corticostriatal pathway. Here, we review a number of ASD-associated high-confidence genes, including FMR1, KMT2A, GRIN2B, SCN2A, NLGN1, NLGN3, MET, CNTNAP2, FOXP2, TSHZ3, SHANK3, PTEN, CHD8, MECP2, DYRK1A, RELN, FOXP1, SYNGAP1, and NRXN, and discuss their relevance to proper corticostriatal function.

Keywords: autism spectrum disorders; corticostriatal pathway; long-term depression; long-term potentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology*
  • Cerebral Cortex / physiopathology*
  • Child
  • Corpus Striatum / physiopathology*
  • Gene Expression Regulation / genetics
  • Humans
  • Neural Pathways / physiopathology*
  • Reelin Protein