QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (38) Citing Articles via Google Scholar Google Scholar Articles by Kim, J.-H. Articles by Rowan, M. J. Search for Related Content PubMed PubMed Citation Articles by Kim, J.-H. Articles by Rowan, M. J.

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 15, 2001, 21(4):1327-1333

Use-Dependent Effects of Amyloidogenic Fragments of -Amyloid Precursor Protein on Synaptic Plasticity in Rat Hippocampus In Vivo

Joung-Hun Kim¹, Roger Anwyl², Yoo-Hun Suh³, Mustafa B. A. Djamgoz⁴, and Michael J. Rowan¹

Departments of ¹ Pharmacology and Therapeutics and ² Physiology, Trinity College, Dublin 2, Ireland, ³ Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia Research Institute, Medical Research Center, Seoul National University, Seoul 110-799, Korea, and ⁴ Department of Biology, Imperial College, London SW7 2AZ, United Kingdom

The Alzheimer's disease-related -amyloid precursor protein (-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 -amyloid peptide (A1-42) and the A-containing C -terminus of -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 A1-42, it induced an LTD that was blocked by D-()-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.

Key words: Alzheimer's disease; long-term potentiation (LTP); long-term depression (LTD); depotentiation; amyloid  peptide (A); C terminus fragment; -amyloid precursor protein (-APP)

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/2141327-07$05.00/0

This article has been cited by other articles:

				M. Townsend, G. M. Shankar, T. Mehta, D. M. Walsh, and D. J. Selkoe Effects of secreted oligomers of amyloid {beta}-protein on hippocampal synaptic plasticity: a potent role for trimers J. Physiol., April 15, 2006; 572(2): 477 - 492. [Abstract] [Full Text] [PDF]

				D. Zhao, J. B. Watson, and C.-W. Xie Amyloid {beta} Prevents Activation of Calcium/Calmodulin-Dependent Protein Kinase II and AMPA Receptor Phosphorylation During Hippocampal Long-Term Potentiation J Neurophysiol, November 1, 2004; 92(5): 2853 - 2858. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help