Alzheimer β-amyloid blocks epileptiform activity in hippocampal neurons

Several studies showed that hippocampal neurons respond with an increase in synaptic transmission after chronic blockade of GABA(A) receptors with bicuculline, a neuroplastic phenomenon likely associated to epileptiform states. Here, we tested the effect of A beta(1-40) 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 A beta(1-40) aggregates. Data suggest that A beta aggregates exert their influence principally by blocking synaptic transmission and altering the transcriptional pathway associated with CREB-p. In conclusion, neurons exposed to aggregated A beta(1-40) showed a reduced level of neuronal plasticity and this suggests that they might be acting as anti-epileptiform modulators. (c) 2009 Elsevier Inc. All rights reserved.