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Neural Plasticity
Volume 2014 (2014), Article ID 584314, 12 pages
Research Article

Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors

1Department of Medical Chemistry, University of Szeged, Szeged 6726, Hungary
2Biological Research Center—Biochemistry, Hungarian Academy of Sciences, Temesvari Körút 32, Szeged 6726, Hungary

Received 13 June 2014; Revised 5 August 2014; Accepted 17 August 2014; Published 3 September 2014

Academic Editor: Lucas Pozzo-Miller

Copyright © 2014 Edina Varga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Neuronal hyperexcitability is a phenomenon associated with early Alzheimer’s disease. The underlying mechanism is considered to involve excessive activation of glutamate receptors; however, the exact molecular pathway remains to be determined. Extracellular recording from the CA1 of hippocampal slices is a long-standing standard for a range of studies both in basic research and in neuropharmacology. Evoked field potentials (fEPSPs) are regarded as the input, while spiking rate is regarded as the output of the neuronal network; however, the relationship between these two phenomena is not fully clear. We investigated the relationship between spontaneous spiking and evoked fEPSPs using mouse hippocampal slices. Blocking AMPA receptors (AMPARs) with CNQX abolished fEPSPs, but left firing rate unchanged. NMDA receptor (NMDAR) blockade with MK801 decreased neuronal spiking dose dependently without altering fEPSPs. Activating NMDARs by small concentration of NMDA induced a trend of increased firing. These results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous firing is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased firing activity without modifying evoked fEPSPs. This hyperexcitation was prevented by ifenprodil, an antagonist of the NR2B NMDARs. Overall, these results suggest that Abeta(1-42) induced neuronal overactivity is not dependent on AMPARs but requires NR2B.