TY - JOUR AU - Varga, Edina AU - Juhász, Gábor AU - Bozsó, Zsolt AU - Penke, Botond AU - Fülöp, Lívia AU - Szegedi, Viktor TI - Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors JF - NEURAL PLASTICITY J2 - NEURAL PLAST VL - 2014 PY - 2014 PG - 12 SN - 2090-5904 DO - 10.1155/2014/584314 UR - https://m2.mtmt.hu/api/publication/2755870 ID - 2755870 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Orbán, Gergely AU - Völgyi, Katalin AU - Juhász, Gábor Dénes AU - Penke, Botond AU - Kékesi, Adrienna Katalin AU - Kardos, József AU - Czurkó, András TI - Different electrophysiological actions of 24- and 72-hour aggregated amyloid-beta oligomers on hippocampal field population spike in both anesthetized and awake rats JF - BRAIN RESEARCH J2 - BRAIN RES VL - 1354 PY - 2010 SP - 227 EP - 235 PG - 9 SN - 0006-8993 DO - 10.1016/j.brainres.2010.07.061 UR - https://m2.mtmt.hu/api/publication/1412694 ID - 1412694 AB - Diffusible oligomeric assemblies of the amyloid β-protein (Aβ) could be the primary factor in the pathogenic pathway leading to Alzheimer's disease (AD). Converging lines of evidence support the notion that AD begins with subtle alterations in synaptic efficacy, prior to the occurrence of extensive neuronal degeneration. Recently, however, a shared or overlapping pathogenesis for AD and epileptic seizures occurred as aberrant neuronal hyperexcitability, as well as nonconvulsive seizure activity were found in several different APP transgenic mouse lines. This generated a renewed attention to the well-known comorbidity of AD and epilepsy and interest in how Aβ oligomers influence neuronal excitability. In this study therefore, we investigated the effect of various in vitro-aged Aβ(1-42) oligomer solutions on the perforant pathway-evoked field potentials in the ventral hippocampal dentate gyrus in vivo. Firstly, Aβ oligomer solutions (1 μl, 200 μM) which had been aggregated in vitro for 0, 24 or 72 h were injected into the hippocampus of urethane-anesthetized rats, in parallel with in vitro physico-chemical characterization of Aβ oligomerization (atomic force microscopy, thioflavin-T fluorescence). We found a marked increase of hippocampal population spike (pSpike) after injection of the 24-h Aβ oligomer solution and a decrease of the pSpike amplitude after injection of the 72-h Aβ oligomer. Since urethane anesthesia affects the properties of hippocampal evoked potentials, we repeated the injection of these two Aβ oligomer solutions in awake, freely moving animals. Evoked responses to perforant pathway stimulation revealed a 70% increase of pSpike amplitude 50 min after the 24-h Aβ oligomer injection and a 55% decrease after the 72-h Aβ oligomer injection. Field potentials, that reflect synaptic potentials, were not affected by the Aβ injection. These results demonstrate that oligomeric Aβ aggregates elicit opposite electrophysiological effects on neuronal excitability which depend on their degree of oligomerization. © 2010 Elsevier B.V. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Minkeviciene, R AU - Rheims, S AU - Dobszay, Márton Benedek AU - Zilberter, M AU - Hartikainen, J AU - Fülöp, Lívia AU - Penke, Botond AU - Zilberter, Y AU - Harkany, T AU - Pitkanen, A AU - Tanila, H TI - Amyloid beta-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy JF - JOURNAL OF NEUROSCIENCE J2 - J NEUROSCI VL - 29 PY - 2009 IS - 11 SP - 3453 EP - 3462 PG - 10 SN - 0270-6474 DO - 10.1523/JNEUROSCI.5215-08.2009 UR - https://m2.mtmt.hu/api/publication/246935 ID - 246935 AB - Alzheimer's disease is associated with an increased risk of unprovoked seizures. However, the underlying mechanisms of seizure induction remain elusive. Here, we performed video-EEG recordings in mice carrying mutant human APPswe and PS1dE9 genes (APdE9 mice) and their wild-type littermates to determine the prevalence of unprovoked seizures. In two recording episodes at the onset of amyloid beta (A beta) pathogenesis (3 and 4.5 months of age), at least one unprovoked seizure was detected in 65% of APdE9 mice, of which 46% had multiple seizures and 38% had a generalized seizure. None of the wild-type mice had seizures. In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k immunoreactivity in dentate granular cells and ectopic expression of neuropeptide Y in mossy fibers. In APdE9 mice, persistently decreased resting membrane potential in neocortical layer 2/3 pyramidal cells and dentate granule cells underpinned increased network excitability as identified by patch-clamp electrophysiology. At stimulus strengths evoking single-component EPSPs in wild-type littermates, APdE9 mice exhibited decreased action potential threshold and burst firing of pyramidal cells. Bath application (1h) of A beta 1-42 or A beta 25-35 (proto-) fibrils but not oligomers induced significant membrane depolarization of pyramidal cells and increased the activity of excitatory cell populations as measured by extracellular field recordings in the juvenile rodent brain, confirming the pathogenic significance of bath-applied A beta(proto-) fibrils. Overall, these data identify fibrillar A beta as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity. LA - English DB - MTMT ER - TY - JOUR AU - Molnar, Z AU - Soós, Katalin AU - Lengyel, Imre AU - Penke, Botond AU - Szegedi, Viktor AU - Budai, D TI - Enhancement of NMDA responses by ß-amyloid peptides in the hippocampus in vivo JF - NEUROREPORT J2 - NEUROREPORT VL - 15 PY - 2004 IS - 10 SP - 1649 EP - 1652 PG - 4 SN - 0959-4965 DO - 10.1097/01.wnr.0000134471.06244.d2 UR - https://m2.mtmt.hu/api/publication/247687 ID - 247687 N1 - cited By 45 LA - English DB - MTMT ER - TY - JOUR AU - Harkany, T AU - Ábrahám, István AU - Timmerman, W AU - Laskay, Gábor AU - Tóth, B AU - Sasvári, M AU - Kónya, C AU - Sebens, JB AU - Korf, J AU - Nyakas, Csaba AU - Zarándi, Márta AU - Soós, Katalin AU - Penke, Botond AU - Luiten, PGM TI - β-Amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis JF - EUROPEAN JOURNAL OF NEUROSCIENCE J2 - EUR J NEUROSCI VL - 12 PY - 2000 IS - 8 SP - 2735 EP - 2745 PG - 11 SN - 0953-816X DO - 10.1046/j.1460-9568.2000.00164.x UR - https://m2.mtmt.hu/api/publication/109099 ID - 109099 LA - English DB - MTMT ER -