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Subunits of GABAA Receptor Regulates Inhibitory Synaptic Strength
1 Interdisciplinary Program in Neuroscience, Georgetown University Medical School, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: svicin01{at}georgetown.edu.
Distinct 
subunit subtypes in the molecular assembly of GABAA receptors are a critical determinant of the functional properties of inhibitory synapses. We investigated the contribution of these subunits to the developmental changes of inhibitory synapses in cerebellar granule neurons in primary cultures from wild type and 1 subunit -/- mice. The decay time of mIPSCs halved between 6 days in vitro (DIV) and DIV12. This was paralleled by the decrease of 2 and 3 subunits, the increase of 1 and 6 subunits expression at synapses and changes in the action of selective subunit modulators. A small, but significant shortening of mIPSCs was observed with development in cells from -/- mice together with a decrease in the expression of 3 subunit. In contrast, the expression of 2 subunit at inhibitory synapses in -/- cells was significantly higher than in +/+ cells at DIV 11-12. 5 subunit was not detected and increased sensitivity to a selective 4/6 subunit agonist suggests increased expression of extrasynaptic receptors in -/- mice. 
2/3 subunit expression and loreclezole sensitivity increased with development in +/+, but not in -/- cells, supporting the preferential association of the 1 with the 2 subunit. Synaptic charge transfer strongly decreased with development, but was not different between cells in the +/+ and -/- groups until DIV11-12. Our results uncover a pattern of sequential expression of subunits underlying the changes in functional efficacy of GABAergic networks with development.
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