POTENTIATION OF GABAERGIC SYNAPTIC TRANSMISSION BY AMPA RECEPTORS IN MOUSE CEREBELLAR STELLATE CELLS - CHANGES DURING DEVELOPMENT

1. The effects of low concentrations of domoate, an agonist at both lp ha-amino-3-hydroxy-5-metylisoxazole-4-propionate and kainate receptors (AMPARs and KARs, respectively), were investigated in stellate cells in slices of mouse cerebellum at two developmental stages (postnatal d ay (PN) 11-13 and PN21-25). 2. Low concentrations of domoate enhanced the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin (TTX) at PN11-13 but not at PN21-25. 3. The effects of lo w concentrations of domoate on synaptic activity were probably mediate d by the activation of AMPARs and not KARs, since they were blocked by GYKI 53655 (LY300168), a selective AMPAR antagonist. 4. Domoate incre ased mIPSC frequency in part by activation of presynaptic voltage-depe ndent Ca2+ channels since potentiation was reduced by 60% in the prese nce of Cd2+. AMPARs in stellate cells were found to be permeable to Ca 2+. The residual potentiation in the presence of Cd2+ could thus be du e to a direct entry of Ca2+ through AMPAR channels. 5. In the presence of TTX, potentiation of synaptic activity by focal application of dom oate was not restricted to the region of the cell body but was observe d within distances of 120 mu m. These experiments also revealed a stro ng spatial correlation between the location of the presynaptic effects of domoate and the activation of postsynaptic AMPARs. 6. Our data sho w a developmentally regulated presynaptic potentiation of synaptic tra nsmission between cerebellar interneurones mediated by AMPARs. We disc uss the possibility that the developmental switch could be due to a sh ift in the localization of AMPARs from the axonal to the somato-dendri tic compartment.