Amyloid β-Protein Fragments 25-35 and 31-35 Potentiate Long-Term Depression in Hippocampal CA1 Region of Rats In Vivo

Amyloid beta-protein (A beta) is thought to be responsible for the deficit of learning and memory in Alzheimer's disease (AD), possibly through interfering with synaptic plasticity in the brain. It has been reported that A beta fragments suppress the long-term potentiation (LTP) of synaptic transmission. However, it is unclear whether A beta fragments can regulate long-term depression (LTD), an equally important form of synaptic plasticity in the brain. The present study investigates the effects of A beta fragments on LTD induced by low frequency stimulation (LFS) in the hippocampus in vivo. Our results showed that (1) prolonged 1-10 Hz of LFS all effectively elicited LTD, which could persist for at least 2 h and be reversed by high frequency stimulation (HFS); (2) the effectiveness of LTD induction depended mainly on the number of pulses but not the frequency of LFS; (3) pretreatment with A beta fragment 25-35 (A beta(25-35), 12.5 and 25 nmol) did not change baseline field excitatory postsynaptic potentials but dose-dependently potentiated LTD; (4) A beta fragment 31-35 (A beta(31-35)), a shorter A beta fragment than A beta(25-35), also dose-dependently strengthened LFS-induced hippocampal LTD. Thus, the present study demonstrates the enhancement of hippocampal LTD by A beta in in vivo condition. We propose that A beta-induced potentiation of LTD, together with the suppression of LTP, will result in the impairment of cognitive function of the brain. Synapse 63:206-214, 2009. (C) 2008 Wiley-Liss. Inc.