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Volume 16, Number 11, Issue of June 1, 1996 pp. 3630-3640
Copyright ©1996 Society for Neuroscience

Developmental Changes of Inhibitory Synaptic Currents in Cerebellar Granule Neurons: Role of GABA_A Receptor 6 Subunit

Received Dec. 21, 1995; revised Feb. 27, 1996; accepted March 8, 1996.

Sutthichai Tia², Jin Feng Wang¹, Naiphinich Kotchabhakdi², and Stefano Vicini¹

¹ Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007, and ² Neurobehavioral Biology Center, Mahidol University, Nakorn Pathom 73170, Thailand

Eye opening and increased motor activity after the second postnatal week in rats imply an extensive development of motor control and coordination. We show a parallel developmental change in spontaneous IPSC (sIPSC) kinetics in cerebellar granule neurons. sIPSCs were studied by whole-cell recordings in cerebellar slices, prepared from 7-30 postnatal day old rats. Early in development, sIPSCs had slow decay kinetics whereas in older rats faster decaying sIPSCs were found in larger proportion. Currents elicited by 1 mM GABA pulses (GABACs) in nucleated patches excised from cerebellar granule neurons revealed that GABACs kinetics better approximate sIPSC decay in young but not in more developed rats. The expression of 6 subunit of GABA_A receptors, unique in cerebellar granule neurons, has been shown to increase during development. Therefore, we took advantage of the recently reported selective inhibition of GABA_A receptors by furosemide to characterize the relative contribution of 6 subunits to native receptors in inhibitory synapses of cerebellar granule neurons. Although furosemide inhibition of sIPSCs amplitude was highly variable among distinct granule cells, it increased during development. At the same time, furosemide failed to inhibit sIPSCs recorded from Purkinje neurons. From the comparison of furosemide inhibition and kinetics of sIPSCs with GABACs recorded from mammalian HEK293 cells transfected with combinations of 1 and 6 GABA_A receptor subunits together with 22 subunits, we propose that an increased 6 subunit contribution in the molecular assembly of postsynaptic receptors in cerebellar glomeruli is responsible for the developmental changes observed.

Key words: cerebellum; patch clamp; inhibitory synapses; development; GABA channels; furosemide

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