The Role of Actin Depolymerization in the Mechanisms of Long-Term Potentiation
摘要
Changes in the dynamics of post-tetanic modifications following high-frequency stimulation of Schaffer collaterals were studied in field CA1 of rat hippocampal slices on the background of blockade of actin depolymerization. Tetanization in the experimental group of slices was performed after application of the actin depolymerization inhibitor jasplakinolide. Jasplakinolide was discontinued from the perfusion solution 15 min after tetanization to exclude its influence during the long-term potentiation (LTP) maintenance phase. The experiments tested the suggestion that blockade of actin depolymerization might impede the consolidation of long-term rearrangements of synaptic transmission. The results showed that 1 h after tetanization in the presence of jasplakinolide, the percentage increase in response amplitude was significantly smaller than that in the control group, though the decrease in early LTP did not allow a definitive link between this effect and disruption of the mechanisms of consolidation of LTP to be established. Drug effects specific to the consolidation process were assessed by correlation analysis, along with a set of transformations allowing neutralization of the contribution of the factor consisting of deficit of early LTP. The results showed that at a given, even quite high, level of early potentiation, the depotentiation often seen during tetanization at 100 Hz for 1 sec was absent from the experimental group but not from the control group. This finding may point to an improvement in the maintenance of LTP, albeit at a lower level as compared with controls. Other indicators which take account of differences in the level of early potentiation suggested that the maintenance of LTP at least did not worsen. These results do not confirm – though they do not refute – the hypothesis that actin depolymerization is required for the consolidation of long-term rearrangements of synaptic transmission. It is suggested that in conditions of blockade of actin depolymerization, maintenance of potentiation may be supported by local protein synthesis in dendrites.