Abstract

Several studies showed that hippocampal neurons respond with an increase in synaptic transmission after chronic blockade of GABAA receptors with bicuculline, a neuroplastic phenomenon likely associated to epileptiform states. Here, we tested the effect of Aß1-40 oligomers/aggregates, believed to be involved in Alzheimer's Disease (AD) genesis, on this type of synaptic plasticity. In the presence of bicuculline, the frequency of miniature currents increased from 1.2 ± 0.4 Hz to 3.1 ± 0.6 Hz (n = 6, *p < 0.05). Similarly, current amplitude increased from 45 ± 3 pA to 81 ± 11 pA (n = 5, *p < 0.05). These effects were completely inhibited in the presence of Aß1-40 aggregates. Data suggest that Aß aggregates exert their influence principally by blocking synaptic transmission and altering the transcriptional pathway associated with CREB-p. In conclusion, neurons exposed to aggregated Aß1-40 showed a reduced level of neuronal plasticity and this suggests that they might be acting as anti-epileptiform modulators. © 2009 Elsevier Inc. All rights reserved.