Abstract
Recent evidence indicates the presence of presynaptic GABAA receptors (GABAARs) in the axon domain of several classes of central neurons, including cerebellar basket and stellate cells. Here, we investigate the possibility that these receptors could be activated in the absence of electrical or chemical stimulation. We find that low concentrations of GABA increase the frequency of miniature GABAergic synaptic currents. Submaximal concentrations of a GABAAR blocker, gabazine, decrease both the miniature current frequency and the probability of evoked GABA release. Zolpidem, an agonist of the benzodiazepine binding site, and NO-711 (1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride), a blocker of GABA uptake, both increase the frequency of miniature currents. These effects occur up to postnatal day 14, but not later. Immunohistochemistry indicates the presence of α1-containing GABAARs in interneuron presynaptic terminals with a similar age dependence. We conclude that, under resting conditions, axonal GABAARs are significantly activated, that this activation results in enhanced GABA release, and that it can be augmented by increasing the affinity of GABAARs or reducing GABA uptake. Our findings suggest the existence of a positive-feedback mechanism involving presynaptic GABAARs that maintains a high release rate and a high local GABA concentration in the immature cerebellar network.