title: Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein.
abstract: 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.
authors.affiliation: Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, United States.
authors.forename: Leah
authors.initials: L
authors.lastname: Selby
authors.forename: Chunzhao
authors.initials: C
authors.lastname: Zhang
authors.forename: Qian-Quan
authors.initials: QQ
authors.lastname: Sun
mesh_terms: D000818:Animals; D002452:Cell Count; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology*; D009415:Nerve Net / Q000166:cytology*; D009433:Neural Inhibition / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D010320:Parvalbumins; D020813:Receptor, trkB; D005680:gamma-Aminobutyric Acid