Expression and Rapid Experience-Dependent Regulation of Type-A GABAergic Receptors in the Songbird Auditory Forebrain
DEVELOPMENTAL NEUROBIOLOGY
Authors: Jeong, Jin Kwon; Terleph, Thomas A.; Burrows, Kaiping; Tremere, Liisa A.; Pinaud, Raphael
Abstract
GABAergic transmission influences sensory processing and experience-dependent plasticity in the adult brain. Little is known about the functional organization of inhibitory circuits in the auditory forebrain of songbirds, a robust model extensively used in the study of central auditory processing of behaviorally relevant communication signals. In particular, no information is currently available on the expression and organization of GABA(A) receptor-expressing neurons. Here, we studied the distribution and regulation of GABA(A) receptors in the songbird auditory forebrain, with a specific focus on alpha 5, a subunit implicated in tonic inhibition and sensory learning. We obtained a zebra finch cDNA that encodes the alpha 5-subunit (GABRA5) and carried out a detailed analysis of its expression via in situ hybridization. GABRA5 was highly expressed in the caudomedial nidopallium (NCM), caudomedial meso-pallium, and field L2. Using double fluorescence in situ hybridization, we demonstrate that a large fraction of GABRA5-expressing neurons is engaged by auditory experience, as revealed by the song-induced expression of the activity-dependent gene zenk. Remarkably, we also found that alpha 5 expression is rapidly regulated by sensory stimulation: 30 min of conspecific song playbacks significantly increase the number of GABRA5-expressing neurons in NCM, but not in other auditory areas. This effect is selective for alpha 5, but not gamma 2 transcripts. Our results suggest that alpha 5-containing GABA(A) receptors likely play a key role in central auditory processing and may contribute to the experience-dependent plasticity underlying auditory learning. (C) 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 803-817, 2011
Gene-wide tagging study of the effects of common genetic polymorphisms in the a subunits of the GABA(A) receptor on epilepsy treatment response
PHARMACOGENOMICS
Authors: Hung, Chin-Chuan; Chen, Pei-Lung; Huang, Wan-Min; Tai, John Jen; Hsieh, Tsung-Jen; Ding, Shih-Torng; Hsieh, Yow-Wen; Liou, Horng-Huei
Abstract
Aim: We aimed to identify the effect of SNPs in the -subunits of GABA(A) receptors on epilepsy treatment outcomes by using a gene-wide tagging method. Materials & methods: There were 720 epileptic patients included in the present study. A total of 136 tagging SNPs in GABRA1, GABRA2, GABRA3, GABRA4, GABRA5 and GABRA6 were genotyped by Illumina((R))GoldenGate((R)) Genotyping platform. Clinical information, such as prescribed antiepileptic drugs, height, weight, epilepsy syndrome classification, etiology, number of attacks, renal function and liver function were collected. The associations between SNPs and epilepsy treatment outcomes were analyzed using SAS((R)) version 9.1.3. Both multivariate logistic regression and multifactor dimensionality reduction analyses were performed. Results: The results of single gene effects did not remain significant after Bonferroni's corrections. Further multivariate logistic regression and multifactor dimensionality reduction analyses of interactions between these genes showed that under adjustment of clinical factors, the epilepsy treatment outcomes were significantly associated with the genotype combinations of GABRA1 rs6883877, GABRA2 rs511310 and GABRA3 rs4828696 (p < 0.0001; adjusted r(2) = 0.149). Conclusion: Our results indicated that genetic variants in the subunits of GABA(A) receptors may interactively affect the treatment responses of antiepileptic drugs. Further replication using an independent sample collection would be essential to confirm our findings. Original submitted 13 June 2013; Revision submitted 12 August 2013