GABA(A) receptor alpha 1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons

Developmental changes in miniature IPSC (mIPSC) kinetics have been demonstr ated previously in cerebellar neurons in rodents. We report that these kine tic changes in mice are determined primarily by developmental changes in GA BAA receptor subunit expression. mIPSCs were studied by whole-cell recordin gs in cerebellar slices, prepared from postnatal day 11 (P11) and P35 mice. Similar to reports in granule neurons, wild-type cerebellar stellate neuro n mIPSCs at P11 had slow decay kinetics, whereas P35 mIPSCs decayed five ti mes faster. When mIPSCs in cerebellar stellate neurons were compared betwee n wild-type (+/+) and GABA(A) receptor alpha1 subunit-deficient (-/-) litte rmates at P35, we observed dramatically slower mIPSC decay rates in -/- ani mals. We took advantage of the greater potency of imidazopyridines for GABA current potentiation with alpha1 subunit-containing receptors to character ize the relative contribution of alpha1 subunits in native receptors on inh ibitory synapses of cerebellar granule neurons. Zolpidem-induced prolongati on of mIPSC decay was variable among distinct cells, but it increased durin g development in wild-type mice. Similarly, Zolpidem prolongation of mIPSC decay rate was significantly greater in adult +/+ mice than in knock-outs. We propose that an increased alpha1 subunit assembly in postsynaptic recept ors of cerebellar inhibitory synapses is responsible for the fast inhibitor y synaptic currents that are normally observed during postnatal development .