Elsevier

Neuroscience Letters

Volume 412, Issue 3, 2 February 2007, Pages 227-232
Neuroscience Letters

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

https://doi.org/10.1016/j.neulet.2006.11.062Get rights and content

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.

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Acknowledgement

Leah Selby is a recipient of NSF-Wyoming–EPSCoR summer and fall undergraduate research fellowship award. This research was made possible by NIH-NCRR grant P20 RR16474-04. Confocal microscopy was performed in the University of Wyoming's Microscopy Core Facility. We thank Dr. William T. Greenough at the University of Illinois, Urbana, for generously providing the first generation of FMR1KO mice and their background WT strain and for providing genotyping protocols.

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