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Title: Expression of GABAA receptor subunit genes in the avian song system and their role in learning and memory
Author: Poole, A.
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2010
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γ-aminobutyric acid type A (GABAA) receptors are the primary mediators of inhibitory neurotransmission in the brain. In avian systems, 14 GABAA receptor subunits (α1-6; β2-β4; γ1, 2 and 4, δ and π) have been identified. These assemble into pentameric transmembrane structures with an intrinsic chloride-selective pore and are involved in the modulation of learning and memory. Following imprinting training in the one-day old chicken, mRNA encoding the GABAA receptor γ4 subunit is significantly reduced in learning-relevant brain regions indicating a role for receptors comprising this subunit in learning and memory. The zebra finch (Taenopygia guttata) song system has long since been used as a paradigm for studying the underlying molecular mechanisms of learning and memory due to the discrete nature of song, the song system and established stages in song development. The avian brain displays many comparable structures and pathways to mammalian systems and there are striking parallels between birdsong and speech production in humans hence the fundamental neuronal mechanisms are similar. Despite major developments towards understanding the anatomical and electrophysiological properties of various song-system nuclei, the nature of the underlying molecular and biochemical/genetic architecture remains largely unknown. Electrophysiological and pharmacological techniques have localised GABAA receptors in the song system and more recently the spatial distribution of γ4-subunit mRNA has been mapped, producing striking results. This had inspired this study (the first of its kind in zebra finch) to isolate all complementary DNAs for zebra finch α1-6; β2-β4; γ1, γ2, γ4, δ and π subunits and characterise their expression in this learning and memory paradigm. Radioactive in situ hybridisation was employed to quantitatively map all GABAA receptor subunits within four important nuclei of the song system (LMAN, Area X, HVC and RA) and revealed region-specific transcription of genes; each subunit exhibiting an individual expression profile in brain, indicative of a variety of major and minor subtype assemblies. Real-time RT-PCR confirmed developmentally-associated subunit mRNA levels in all song-system nuclei. γ4-subunit mRNA exhibited the most robust expression and coordinated peaks of mRNA expression at specific developmental time points in the relevant nuclei, subsequently expression of the γ4-subunit mRNA was examined in a behavioural context. Corresponding mRNA was down-regulated in response to acquisition and production of song (not evident with γ2-subunit mRNA), indicative of a specialised role for these receptors in cognitive processes. Preliminary in vitro RNA interference experiments indicated that γ4-subunit gene expression could be reduced in chicken neurons, paving the way for in vivo gene silencing experiments in zebra finch.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available