Alterations in GABAA receptor occupancy occur during the postnatal development of rat Purkinje cell but not granule cell synapses

The identification of synaptic GABA(A) receptors has proved difficult as neurones express multiple GABA(A) receptor subunits. For example, cerebellar granule cells express alpha 1, alpha 6, gamma 2, delta and beta 2/3 subunits and thus express many different GABA(A) receptor subtypes. Furthermore, the contribution of individual GABAA receptor subtypes is changed by developmental alterations in subunit expression. To further characterise the pharmacology of Golgi cell to granule cell synapses during development, the benzodiazepine-site ligand zolpidem was used. Zolpidem shows selectivity for alpha 1 beta x gamma 2 receptors (x is any beta subunit) and slows the decay and enhances the amplitude of (xloxy2 receptor-mediated synaptic currents, provided the receptors are not fully occupied. For comparison, zolpidem was applied to Purkinje cell synapses, since the synaptic receptors are of known composition (alpha 1 beta x gamma 2). At immature and adult Golgi cell to granule cell synapses, the decay of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) was slowed by zolpidem but their amplitude and frequency were unaffected. At Purkinje cell synapses, although zolpidem slowed the decay of IPSCs at both immature and adult synapses, zolpidem only enhanced the amplitude of IPSCs at adult synapses. Thus during development, the level of receptor occupation remains constant at Golgi cell to granule cell synapses but falls at Purkinje cell synapses. (c) 2005 Elsevier Ltd. All rights reserved.