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The Journal of Neuroscience, May 1, 2001, 21(9):3009-3016

GABA_A Receptor 1 Subunit Deletion Prevents Developmental Changes of Inhibitory Synaptic Currents in Cerebellar Neurons

Stefano Vicini¹, Carolyn Ferguson², Kate Prybylowski¹, Jason Kralic³, A. Leslie Morrow³, and Gregg E. Homanics²

¹ Department of Physiology and Biophysics, Georgetown University Medical School, Washington, DC 20007, ² Departments of Anesthesiology/Critical Care Medicine and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and ³ Department of Psychiatry and Pharmacology, University of North Carolina Medical School, Chapel Hill, North Carolina 27599-7178

Developmental changes in miniature IPSC (mIPSC) kinetics have been demonstrated previously in cerebellar neurons in rodents. We report that these kinetic changes in mice are determined primarily by developmental changes in GABA_A receptor subunit expression. mIPSCs were studied by whole-cell recordings in cerebellar slices, prepared from postnatal day 11 (P11) and P35 mice. Similar to reports in granule neurons, wild-type cerebellar stellate neuron mIPSCs at P11 had slow decay kinetics, whereas P35 mIPSCs decayed five times faster. When mIPSCs in cerebellar stellate neurons were compared between wild-type (+/+) and GABA_A receptor 1 subunit-deficient (/) littermates at P35, we observed dramatically slower mIPSC decay rates in / animals. We took advantage of the greater potency of imidazopyridines for GABA current potentiation with 1 subunit-containing receptors to characterize the relative contribution of 1 subunits in native receptors on inhibitory synapses of cerebellar granule neurons. Zolpidem-induced prolongation of mIPSC decay was variable among distinct cells, but it increased during 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 1 subunit assembly in postsynaptic receptors of cerebellar inhibitory synapses is responsible for the fast inhibitory synaptic currents that are normally observed during postnatal development.

Key words: GABA receptor; gene knock-out; patch-clamp; inhibitory synapses; development; GABA

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Copyright © 2001 Society for Neuroscience  0270-6474/01/2193009-08$05.00/0

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