Research Article Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors Edina Varga, 1 Gábor Juhász, 1 Zsolt Bozsó, 1 Botond Penke, 1 Lívia Fülöp, 1 and Viktor Szegedi 2 1 Department of Medical Chemistry, University of Szeged, Szeged 6726, Hungary 2 Biological Research Center—Biochemistry, Hungarian Academy of Sciences, Temesvari K¨ or´ ut 32, Szeged 6726, Hungary Correspondence should be addressed to Viktor Szegedi; szegedi.viktor@brc.mta.hu 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. his 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. he 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 ield 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 let iring 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 iring. hese results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous iring is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased iring activity without modifying evoked fEPSPs. his 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. 1. Introduction Extracellular recording from hippocampal slices has long been a method of choice for determining the changes in excitability and synaptic plasticity of the CA1 microcircuitry [1]. Spontaneous spikes and, far more oten, ield excitatory postsynaptic potentials (fEPSPs) are recorded extracellularly from a local network of neurons; however, the relationship between these two phenomena is not fully clear. Intuitively, both electrophysiological events correlate with the excitabil- ity of the network under investigation, but these events are generated by diferent mechanisms. Field EPSPs are mainly composed of subthreshold events from a population of neu- rons, like dendritic depolarizations [2] and glial contributions to the net extracellular charge-low, arising mainly from the function of transporters [3, 4]. In contrast, spontaneous iring represents only neuronal suprathreshold events [5]. Another diference is that a fEPSP is evoked by a stimulus, and therefore it is the result of a coordinated and synchronized electrical activity of a cell population, mediated by synaptic connections. Spontaneous spikes, in contrast, are not evoked by an external stimulus, and they are more likely to be dependent on intrinsic network connections and properties [6]. N-Methyl-D-aspartate receptor (NMDAR) and -Ami- no-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) play a key role in generating rapid excitatory events in the CA1, but these receptors serve diferent purposes. heir relative contribution to fEPSPs is well described [7]; however, their involvement in spontaneous spike-generation remains unknown and data on the correlation of extracellularly recorded ield responses and action potentials are scarce. Activation of glutamate (Glu) receptors is known to play an important role in the mechanisms of neuronal plasticity Hindawi Publishing Corporation Neural Plasticity Volume 2014, Article ID 584314, 12 pages http://dx.doi.org/10.1155/2014/584314