Region-specific alterations in the gene expression of select GABAA receptor subunits in the telencephalon of the adult uPAR-/- mouse

K. L. EAGLESON; M. C. GRAVIELLE; L. MCFADYEN-KETCHUM; S. J. RUSSEK; D. H. FARB; P. LEVITT

EEUU de America

Congreso; XXXVIII Reunion anual de la Society for Neuroscience; 2008

Society for Neuroscience

Disruption of the GABAergic system has been implicated in multiple developmental disorders, including epilepsy, autism spectrum disorder and schizophrenia. The uPAR-/- mouse has a significant reduction in GABAergic interneurons in frontal and parietal regions of the cerebral cortex, as well as in the CA1 and dentate gyrus subfields of the hippocampus. Behaviorally, these mice exhibit an increased sensitivity to pharmacologically-induced convulsions and atypical social behavior. Here, we explored the alterations in GABAergic circuitry that may occur in the telencephalon in the context of altered interneuron development. Analysis of gene expression for 13 GABAA receptor subunits, using real-time PCR, indicated four subunit mRNAs (á2, á3, ã2S and ã2L) of interest. Semi-quantitative in situ hybridization analysis focusing on these subunit mRNAs revealed a complex pattern of potential gene regulatory adaptations. The levels of á2 subunit mRNAs were increased in frontal cortex, CA1 and CA3, while those of á3 were decreased in frontal cortex and CA1. In contrast, ã2S subunit mRNAs were increased in parietal cortex, while ã2L subunit mRNAs were increased in the dentate gyrus, thus potentially altering the ã2S:ã2L ratio in these two regions. No changes were observed in striatum and occipital cortex, in which GABAergic interneuron numbers are normal. We hypothesize that the potential changes in subunit composition occur as an adaptive response to decreased levels of GABA and reflect alterations in network activity in the cortex and hippocampus.