TY - JOUR T1 - Use-Dependent Effects of Amyloidogenic Fragments of β-Amyloid Precursor Protein on Synaptic Plasticity in Rat Hippocampus <em>In Vivo</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1327 LP - 1333 DO - 10.1523/JNEUROSCI.21-04-01327.2001 VL - 21 IS - 4 AU - Joung-Hun Kim AU - Roger Anwyl AU - Yoo-Hun Suh AU - Mustafa B. A. Djamgoz AU - Michael J. Rowan Y1 - 2001/02/15 UR - http://www.jneurosci.org/content/21/4/1327.abstract N2 - The Alzheimer's disease-related β-amyloid precursor protein (β-APP) is metabolized to a number of potentially amyloidogenic peptides that are believed to be pathogenic. Application of relatively low concentrations of the soluble forms of these peptides has previously been shown to block high-frequency stimulation-induced long-term potentiation (LTP) of glutamatergic transmission in the hippocampus. The present experiments examined how these peptides affect low-frequency stimulation-induced long-term depression (LTD) and the reversal of LTP (depotentiation). We discovered that β-amyloid peptide (Aβ1–42) and the Aβ-containing C -terminus of β-APP (CT) facilitate the induction of LTD in the CA1 area of the intact rat hippocampus. The LTD was frequency- and NMDA receptor-dependent. Thus, although low-frequency stimulation alone was ineffective, after intracerebroventricular injection of Aβ1–42, it induced an LTD that was blocked byd-(−)-2-amino-5-phosphonopentanoic acid. Furthermore, an NMDA receptor-dependent depotentiation was induced in a time-dependent manner, being evoked by injection of CT 10 min, but not 1 hr, after LTP induction. These use- and time-dependent effects of the amyloidogenic peptides on synaptic plasticity promote long-lasting reductions in synaptic strength and oppose activity-dependent strengthening of transmission in the hippocampus. This will result in a profound disruption of information processing dependent on hippocampal synaptic plasticity. ER -