Dynamin-1deletion enhances post-tetanic potentiation and quantal size after tetanic stimulation at the calyx of held

High frequency stimulation leads to post-tetanic potentiation (PTP) at many types of synapses. Previous studies suggest that PTP results primarily from a protein kinase C (PKC) dependent increase in release probability (P_r) and/or readily-releasable pool (RRP) of synaptic vesicles (SVs), but the role of SV endocytosis in this process is unknown. Using the mature calyx of Held (P16-20), we reported that the tissue-specific deletion of dynamin-1 (cKO), an endocytic protein crucial for SV regeneration, enhanced PTP compared to control. To explore the mechanism of this enhancement, we estimated the changes of paired-pulse ratios (PPRs) and RRP size during PTP. RRP was estimated by the back extrapolation of cumulative EPSC amplitudes during a train of 30 action potentials at 100 Hz (termed RRP_train). We found an increase in RRP_train during PTP in both control and cKO, but no significant changes in the PPR. Moreover, the amplitude and frequency of spontaneous excitatory postsynaptic currents (spEPSCs) were increased during PTP in both control and cKO; however, the spEPSC amplitude in cKO during PTP was significantly larger than in control. The actin depolymerization reagent Latrunculin-B (Lat-B) abolished the activity-dependent increase in spEPSC amplitude in both control and cKO, but selectively blocked the enhancement of PTP in cKOs without affecting PTP in controls. The PKC inhibitor GF109203X nearly abolished PTP in both control and cKO. These data suggest that the quantal size increase contributes to the enhancement of PTP in dynamin-1 cKO, and this change depends on strong synaptic activity and actin polymerization.

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