Axonal GABA_A receptors increase cerebellar granule cell excitability and synaptic activity

We report that activation of GABA_Areceptors on cerebellar granule cell axons modulates both transmitter release and the excitability of the axon and soma. Axonal GABA_Areceptors depolarize the axon, increasing its excitability and causing calcium influx at axonal varicosities. GABA-mediated subthreshold depolarizations in the axon spread electrotonically to the soma, promoting orthodromic action potential initiation. When chloride concentrations are unperturbed, GABA iontophoresis elicits spikes and increases excitability of parallel fibers, indicating that GABA_Areceptor- mediated responses are normally depolarizing. GABA release from molecular layer interneurons activates parallel fiber GABA_Areceptors, and this, in turn, increases release probability at synapses between parallel fibers and molecular layer interneurons. These results describe a positive feedback mechanism whereby transmission from granule cells to Purkinje cells and molecular layer interneurons will be strengthened during granule cell spike bursts evoked by sensory stimulation.