Inhibition of Calcineurin Decreases Low-Frequency Depression and Increases Long-Term Potentiation in Crayfish Superficial Extensor Muscle Cells

Abstract

Long-term potentiation (LTP) and low-frequency depression (LFD) are two major forms of synaptic plasticity that regulate the strength of neurotransmission. Activities of calcineurin, a Ca²⁺/calmodulin-dependent phosphatase, have been found to be involved in the long-term plasticity at synapses. Studies have established that inhibition of calcineurin blocks the induction of LFD, but questions still remain for specific effects on LTP. To reinforce the effect of calcineurin inhibition on LFD as well as to explore its effect on LTP, we applied the calcineurin inhibitor FK-506 to crayfish neuromuscular junctions undergoing LTP and LFD. Electrical stimulations of 0.2 Hz and 2 Hz were applied through an extracellular microelectrode to trigger LFD and LTP, respectively. We used an intracellular microelectrode to record excitatory post-synaptic potentials (EPSPs) in the superficial extensor muscle cells. Our results showed that after FK-506 was applied, the normalized peak amplitudes of EPSPs decreased under LFD and increased under LTP, supporting our hypothesis that the inhibition of calcineurin would decrease LFD and increase LTP at the neuromuscular junctions of superficial extensor muscle cells.