In Vivo Electrophysiological Study On The Induction Of Hippocampal Long-term Depression (LTD) And Its Modulation By Amyloid β-protein Fragments In Rats

Accumulation and deposition of amyloid-βpeptide (AβP) in brain areas have been widely believed to play a critical role in the pathogenesis of Alzheimer's disease (AD). AβP may be responsible for much of the learning and memory deficit seen early in the disease by interfering with synaptic plasticity in the brain. Application of relatively low concentrations of AβP or some of its fragments (such as AβP25-35) have shown previously to block the high-frequency stimulation (HFS)-induced long-term potentiation (LTP) of synaptic transmission in hippocampus. In our previous studies, AβP31-35, a shorter fragment of AβP, could also suppress the LTP in hippocampus. The present experiments were aimed to investigate the in vivo induction of long-term depression (LTD),another type of cellular model for studying learning and memory, induced by low-frequency stimulation (LFS), examine the optimum parameters of LFS for inducing hippocampal LTD, and observe the possible effects of AβP fragments on LTD.Stimulating electrodes were inserted into the Schaffer's collaterals and extracellular recording electrode was inserted into the stratum radiatum of the hippocampal CA1 region for recording the field excitatory postsynaptic potential (fEPSP) evoked by single electrical stimulation given consecutively with an interval of 30 sec, while AβP31-35 or AβP25-35 were injected into the lateral ventricle on the same side 10 min prior to the delivering of LFS. In applying LFS, four kinds of frequencies, two different pulse numbers in a train and different numbers of train were tested. The results showed that: (1) the average baseline amplitude of fEPSP evoked by test stimulation abruptly decreased to 83.7±2.7% immediately after applying LFS (1 train, 10 Hz, 900 pulses), as compared to that measured before LFS, being set arbitrarily as 100%, the amplitude of fEPSP further decreased to 80.5±3.1% and 74.5±4.1% at 1 hr and 2 hr following LFS respectively; other frequencies (1, 3, and 5 Hz) of LFS could also effectively evoke LTD of fEPSP. (2) the LTD induced by LFS could be reversed by HFS; After using HFS (3 trains, 20 pulses, 200 Hz), the lowered amplitude of fEPSP abruptly returned to 99.7±5.1% from 74.5±4.1% at 2 hr following LFS, being very close to the baseline values before LFS. (3) the effectiveness of LFS-induced LTD seemed to depend mainly on the numbers of pulses in LFS;...