Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein

Neurosci Lett. 2007 Feb 2;412(3):227-32. doi: 10.1016/j.neulet.2006.11.062. Epub 2006 Dec 15.


This study focused on the cytoarchitectonic and morphological differences in GABA-releasing interneurons between adult Fmr1 knock-out (FMR1KO) and wild-type (WT) mice in the somatosensory cortex. Our results showed a robust reorganization of neocortical, but not hippocampal inhibitory circuits in the FMR1KO mouse. The reorganization is characterized by a significant reduction (20%, p<0.001) in the densities of parvalbumin (PV)-positive, but not calbindin (CB) and calretinin (CR)-positive interneurons. A significant enlargement of soma size and an altered lamina distribution of PV but not CR and CB cells was also observed. Additionally, there was a modest but significant increase in TrkB-immunoreactivity in PV-positive cells in the FMR1KO mouse. These results provide the first report showing significant alterations of GABA-releasing interneurons in the mouse model of fragile X syndrome. Uncovering the changes in specific GABAergic inhibitory circuits could help understand mechanisms underlying the behavior deficits of fragile X syndrome and autism.

Publication types

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

MeSH terms

  • Animals
  • Cell Count
  • Fragile X Mental Retardation Protein / genetics*
  • Gene Expression / genetics
  • Interneurons / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neocortex / cytology*
  • Nerve Net / cytology*
  • Neural Inhibition / physiology*
  • Parvalbumins / metabolism
  • Receptor, trkB / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Parvalbumins
  • Fragile X Mental Retardation Protein
  • gamma-Aminobutyric Acid
  • Receptor, trkB