Dysfunctions of cellular context-sensitivity in neurodevelopmental learning disabilities

Neurosci Biobehav Rev. 2024 Jun:161:105688. doi: 10.1016/j.neubiorev.2024.105688. Epub 2024 Apr 25.

Abstract

Pyramidal neurons have a pivotal role in the cognitive capabilities of neocortex. Though they have been predominantly modeled as integrate-and-fire point processors, many of them have another point of input integration in their apical dendrites that is central to mechanisms endowing them with the sensitivity to context that underlies basic cognitive capabilities. Here we review evidence implicating impairments of those mechanisms in three major neurodevelopmental disabilities, fragile X, Down syndrome, and fetal alcohol spectrum disorders. Multiple dysfunctions of the mechanisms by which pyramidal cells are sensitive to context are found to be implicated in all three syndromes. Further deciphering of these cellular mechanisms would lead to the understanding of and therapies for learning disabilities beyond any that are currently available.

Keywords: Apical amplification; Cellular psychology; Context-sensitivity; Dendritic computation; Learning disability; Pyramidal neurons.

Publication types

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

MeSH terms

  • Animals
  • Down Syndrome / physiopathology
  • Fetal Alcohol Spectrum Disorders / physiopathology
  • Fragile X Syndrome / physiopathology
  • Humans
  • Learning Disabilities* / etiology
  • Learning Disabilities* / physiopathology
  • Neurodevelopmental Disorders / physiopathology
  • Pyramidal Cells / physiology