Effect of low intensity low-frequency stimuli on long-term depression in the rat hippocampus area CA1 in vivo

Normally long-term depression (LTD) is difficult to be induced in naïve adult rats in vivo, but it can be induced in the juvenile females and acute-stressed adult males. Using these rats as LTD models, we find in our previous study that LTD induction by the classical low-frequency stimuli (LFS) may be associated with sleep. During sleep, endogenous field potential oscillations presented in the neocortical and hippocampal circuits play important roles in synaptic downscaling as well as memory consolidations. Generally, LTD can be considered as a special synaptic downscaling and the classical LFS is very similar to such endogenous oscillations. Thus, we speculate whether we can design a new LFS which is more similar to such oscillations and whether LTD can be induced by it in naïve adult rats? In this study, we found that in the naïve adult rats anesthetized in sleep stage, the classical LFS could not induce LTD, however, a low-intensity LFS, an endogenous oscillation-like one, could induce LTD. Furthermore, in the rats anesthetized in wakefulness stage, neither the classical nor the low-intensity LFS could induce LTD. Our study showed that in the naïve adult rats, LTD could be induced by the oscillation-like LFS in the sleep stage anesthesia, suggesting that LTD may physiologically occur during sleep and be inhibited in wakefulness stage. Our study suggested that in the hippocampus LTD may be a potential long-term synaptic plasticity underlying sleep-dependent memory consolidations.