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Publication : Knockout of the γ-aminobutyric acid receptor subunit α4 reduces functional δ-containing extrasynaptic receptors in hippocampal pyramidal cells at the onset of puberty.

First Author  Sabaliauskas N Year  2012
Journal  Brain Res Volume  1450
Pages  11-23 PubMed ID  22418059
Mgi Jnum  J:183241 Mgi Id  MGI:5318124
Doi  10.1016/j.brainres.2012.02.035 Citation  Sabaliauskas N, et al. (2012) Knockout of the gamma-aminobutyric acid receptor subunit alpha4 reduces functional delta-containing extrasynaptic receptors in hippocampal pyramidal cells at the onset of puberty. Brain Res 1450:11-23
abstractText  Increased plasmalemmal localization of alpha4betadelta GABA(A) receptors (GABARs) occurs in the hippocampal pyramidal cells of female mice at pubertal onset (Shen et al., 2010). This increase occurs on both dendritic spines and shafts of CA1 pyramidal cells and is in response to hormone fluctuations that occur at pubertal onset. However, little is known about how the alpha4 and delta subunits individually mediate the formation of functional, plasmalemmal alpha4betadelta GABARs. To determine whether expression of the alpha4 subunit is necessary for plasmalemmal delta subunit localization at pubertal onset, electron microscopic-immunocytochemistry (EM-ICC) was employed. CA1 pyramidal cells of female alpha4 knockout (KO) mice were tested for plasmalemmal levels of the delta subunit within dendritic spine and shaft profiles at the onset of puberty. EM-ICC revealed that the alpha4 and delta subunits localize on dendritic spines and shafts at sites extrasynaptic to GABAergic input at pubertal onset in tissue of wild-type (WT) mice. At pubertal onset, plasmalemmal localization of the delta subunit is reduced 45.9% on dendritic spines, and 56.7% on dendritic shafts with KO of the alpha4 subunit, as compared to WT tissue, yet levels of intracellular delta immunoreactivity remain unchanged. The decline in plasmalemmal localization is manifested as decreased responsiveness to the GABA agonist gaboxadol at concentrations that are selective for delta-containing GABARs. Additionally, alpha4 KO mice have larger dendritic spine and shaft profiles. Our findings demonstrate that alpha4 subunit expression strongly influences the pubertal increase of delta subunits at the plasma membrane, and that genetic deletion of alpha4 serves as a functional knock-down of delta-containing GABARs.
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