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The Journal of Neuroscience, May 1, 2001, 21(9):3009-3016
GABAA 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 GABAA 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 GABAA 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
Copyright © 2001 Society for Neuroscience 0270-6474/01/2193009-08$05.00/0
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