Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus

• Published in: Brain research 2002-01, Vol.924 (2), p.133-140
• Main Authors: Wang, Hai-Wei, Pasternak, Joseph F, Kuo, Helen, Ristic, Helen, Lambert, Mary P, Chromy, Brett, Viola, Kirsten L, Klein, William L, Stine, W.Blaine, Krafft, Grant A, Trommer, Barbara L
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - pharmacology; Animals; Aβ-derived diffusible ligand; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dentate gyrus; Dentate Gyrus - physiology; Excitatory Postsynaptic Potentials - drug effects; Female; Long-term depression; Long-term potentiation; Long-Term Potentiation - drug effects; Male; Medical sciences; Neural Inhibition - drug effects; Neurology; Neuronal Plasticity - drug effects; Neuroplasticity; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Solubility; Synapses - physiology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)03058-X

The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (Aβ) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of Aβ possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death. We therefore examined the effects of soluble oligomers of Aβ 1-42 on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of Aβ-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response, slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating ‘neuroplasticity imbalance’ manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP.