Tenuigenin enhances hippocampal Schaffer collateral-CA1 synaptic transmission through modulating intracellular calcium

Background: Tenuigenin (TEN), a natural product from the Chinese herb Polygala tenuifolia root, has been reported to improve cognitive function and exhibits neuroprotective effects in pharmacological studies of the central nervous system. Synaptic transmission is the essential process of brain physiological functions such as learning and memory formation, and TEN has been shown to facilitate the basic synaptic transmission.

Hypothesis/purpose: Although our previous work has demonstrated that TEN is able to potentiate the basic synaptic transmission, the potential mechanism remains unclear. Here we investigated the effect of TEN on the synaptic transmission and analysed the potential mechanism. We hope that these findings will contribute to explain the role of TEN as a nootropic product or neuroprotective drug in the future.

Methods: Field excitatory postsynaptic potentials (fEPSPs), spontaneous excitatory postsynaptic currents (sEPSCs) and miniature spontaneous excitatory postsynaptic currents (mEPSCs) were recorded, by using in vitro field potential electrophysiology and whole-cell patch clamp techniques in acute hippocampal slices from rats.

Results: TEN perfusion significantly enhanced the slope of fEPSPs and reduced the ratio of paired-pulse facilitation. Moreover, TEN increased the frequency and amplitude of sEPSCs but only improved the frequency of mEPSCs rather than amplitude in hippocampal CA1 pyramidal neurons. With removal of extracellular calcium, TEN treatment also enhanced the mEPSCs frequency without affecting amplitude. Interestingly, the increase of mEPSCs frequency caused by TEN was blocked by chelation of intracellular calcium with BAPTA-AM.

Conclusion: These results indicate that TEN enhances the basic synaptic transmission via stimulating presynaptic intracellular calcium.