@article{MTMT:1329681, title = {Controlled in situ preparation of Aβ(1-42) oligomers from the isopeptide "iso-Aβ(1-42)", physicochemical and biological characterization}, url = {https://m2.mtmt.hu/api/publication/1329681}, author = {Bozsó, Zsolt and Penke, Botond and Simon, Dóra and Laczkó, Ilona and Juhász, Gábor and Szegedi, Viktor and Kasza, Ágnes and Soós, Katalin and Hetényi, Anasztázia and Wéber, Edit and Tóháti, Hajnalka-Mária and Czirjákné Csete, Mária and Zarándi, Márta and Fülöp, Lívia}, doi = {10.1016/j.peptides.2009.12.001}, journal-iso = {PEPTIDES}, journal = {PEPTIDES}, volume = {31}, unique-id = {1329681}, issn = {0196-9781}, abstract = {beta-Amyloid (A beta) peptides play a crucial role in the pathology of the neurodegeneration in Alzheimer's disease (AD). Biological experiments (both in vitro and animal model studies of AD) require synthetic A beta peptides of standard quality, aggregation grade, neurotoxicity and water solubility. The synthesis of A beta peptides has been difficult, owing to their hydrophobic character, poor solubility and high tendency for aggregation. Recently an isopeptide precursor (iso-A beta(1-42)) was synthesized by Fmoc-chemistry and transformed at neutral pH to A beta(1-42) by O -> N acyl migration in a short period of time. We prepared the same precursor peptide using Boc-chemistry and studied the transformation to A beta(1-42) by acyl migration. The peptide conformation and aggregation processes were studied by several methods (circular dichroism, atomic force and transmission electron microscopy, dynamic light scattering). The biological activity of the synthetic A beta(1-42) was measured by ex vivo (long-term potentiation studies in rat hippocampal slices) and in vivo experiments (spatial learning of rats). It was proven that O -> N acyl migration of the precursor isopeptide results in a water soluble oligomeric mixture of neurotoxic A beta(1-42). These oligomers; are formed in situ just before the biological experiments and their aggregation grade could be standardized. (C) 2009 Elsevier Inc. All rights reserved.}, keywords = {AGGREGATION; ALZHEIMERS-DISEASE; PROTEIN; SOLID-PHASE SYNTHESIS; AMYLOID-BETA; OLIGOMERS; Alzheimer's disease; DEPROTECTION; PEPTIDE-SYNTHESIS; beta-Amyloid; Endocrinology & Metabolism; Biochemistry & Molecular Biology; DIFFICULT SEQUENCES; A-BETA-1-42 ISOPEPTIDE; PSEUDO-PROLINES}, year = {2010}, eissn = {1873-5169}, pages = {248-256}, orcid-numbers = {Bozsó, Zsolt/0000-0002-5713-3096; Penke, Botond/0000-0003-0938-0567; Szegedi, Viktor/0000-0003-4191-379X; Hetényi, Anasztázia/0000-0001-8080-6992; Wéber, Edit/0000-0002-5904-0619; Czirjákné Csete, Mária/0000-0002-3755-714X; Zarándi, Márta/0000-0002-2136-2946; Fülöp, Lívia/0000-0002-8010-0129} } @article{MTMT:2966603, title = {Use-dependent shift from inhibitory to excitatory GABAA receptor action in SP-O interneurons in the rat hippocampal CA3 area.}, url = {https://m2.mtmt.hu/api/publication/2966603}, author = {Lamsa, Karri and Taira, T}, doi = {10.1152/jn.00060.2003}, journal-iso = {J NEUROPHYSIOL}, journal = {JOURNAL OF NEUROPHYSIOLOGY}, volume = {90}, unique-id = {2966603}, issn = {0022-3077}, abstract = {Cortical inhibitory interneurons set the pace of synchronous neuronal oscillations implicated in synaptic plasticity and various cognitive functions. The hyperpolarizing nature of inhibitory postsynaptic potentials (IPSPs) in interneurons has been considered crucial for the generation of oscillations at beta (15-30 Hz) and gamma (30-100 Hz) frequency. Hippocampal basket cells and axo-axonic cells in stratum pyramidale-oriens (S-PO) play a central role in the synchronization of the local interneuronal network as well as in pacing of glutamatergic principal cell firing. A lack of conventional forms of plasticity in excitatory synapses onto interneurons facilitates their function as stable neuronal oscillators. We have used gramicidin-perforated and whole cell clamp recordings to study properties of GABAAR-mediated transmission in CA3 SP-O interneurons and in CA3 pyramidal cells in rat hippocampal slices during electrical 5- to 100-Hz stimulation and during spontaneous activity. We show that GABAergic synapses onto SP-O interneurons can easily switch their mode from inhibitory to excitatory during heightened activity. This is based on a depolarizing shift in the GABAA reversal potential (EGABA-A), which is much faster and more pronounced in interneurons than in pyramidal cells. We also found that the shift in interneuronal function was frequency dependent, being most prominent at 20- to 40-Hz activation of the GABAergic synapses. After 40-Hz tetanic stimulation (100 pulses), GABAA responses remained depolarizing for approximately 45 s in the interneurons, promoting bursting in the GABAergic network. Hyperpolarizing EGABA-A was restored >60 s after the stimulus train. Similar but spontaneous GABAergic bursting was induced by application of 4-aminopyridine (100 microM) to slices. A shift to depolarizing IPSPs by the GABAAR permeant weak acid anion formate provoked interneuronal population bursting, supporting the role of GABAergic excitation in burst generation. Furthermore, depolarizing GABAergic potentials and synchronous interneuronal bursting were enhanced by pentobarbital (100 microM), a positive allosteric modulator of GABAARs, and were blocked by picrotoxin (100 microM). Intriguingly, GABAergic bursts displayed short (<1 s) oscillations at 15-40 Hz, even though only depolarizing GABAA responses were seen in the SP-O interneurons. This beta-gamma rhythmicity in the interneuron network was dependent on electrotonic coupling, and was abolished by blockade of gap junctions with carbenoxolone (200 microM). Results here implicate the rapid activity-dependent degradation of hyperpolarizing IPSPs in SP-O interneurons in setting the temporal limits for a given interneuron to participate in beta-gamma oscillations synchronized by GABAergic synapses. Furthermore, they imply that mutual GABAergic excitation provided by interneurons may be an integral part in the function of neuronal networks. We suggest that the use-dependent change in EGABA-A could represent a form of short-term plasticity in interneurons promoting coherent and sustained activation of local GABAergic networks.}, keywords = {Animals; RATS; Rats, Wistar; Neural Inhibition/drug effects/physiology; Synaptic Transmission/drug effects/*physiology; Hippocampus/drug effects/*physiology; Biological Clocks/drug effects/*physiology; Interneurons/drug effects/*physiology; Receptors, GABA-A/*physiology}, year = {2003}, eissn = {1522-1598}, pages = {1983-1995}, orcid-numbers = {Lamsa, Karri/0000-0002-4609-1337} } @article{MTMT:31149258, title = {Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus.}, url = {https://m2.mtmt.hu/api/publication/31149258}, author = {Vertes, R P and Kocsis, Bernat}, doi = {10.1016/s0306-4522(97)00239-x}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {81}, unique-id = {31149258}, issn = {0306-4522}, abstract = {We present a new model for the generation of theta rhythm of the hippocampus. We propose that theta at CA1 involves extracellular current fluxes produced by alternating depolarizing and hyperpolarizing membrane potential fluctuations of large populations of hippocampal pyramidal cells. Pyramidal cells are, in turn, controlled by rhythmically bursting cholinergic and GABAergic cells of the medial septum/vertical limb of the diagonal band. We postulate that septal cholinergic and GABAergic rhythmically bursting cells fire in relative synchrony; their coordinated burst discharge (burst mode) drives the positive-going phase of intracellular theta and associated firing of pyramidal cells; their synchronized pauses (interburst mode) give rise to the negative-going phase of intracellular theta and an inhibition of pyramidal cells. We further demonstrate that the theta rhythm is controlled by a network of cells extending from the brainstem to the septum/hippocampus. During theta, tonically discharging cells of the nucleus reticularis pontis oralis activate neurons of the supramammillary nucleus; the supramammillary nucleus, in turn, converts this steady barrage into a rhythmical pattern of discharge which is relayed to GABAergic/ cholinergic rhythmically bursting cells of the medial septum. The septal rhythmically bursting cells modulate subsets of hippocampal interneurons and principal cells in the generation of the theta rhythm. We review evidence showing that the serotonin-containing neurons of the median raphe nucleus desynchronize the hippocampal electroencephalogram, presumably by disrupting the rhythmical discharge of septal cholinergic and GABAergic neurons. Finally, we summarize recent work indicating that the theta rhythm is critically involved in memory functions of the hippocampus and that its disruption (electroencephalographic desynchronization) may block or temporarily suspend mnemonic processes of the hippocampus.}, year = {1997}, eissn = {1873-7544}, pages = {893-926}, orcid-numbers = {Kocsis, Bernat/0000-0003-4371-3249} } @article{MTMT:1428428, title = {GAMMA (40-100-HZ) OSCILLATION IN THE HIPPOCAMPUS OF THE BEHAVING RAT}, url = {https://m2.mtmt.hu/api/publication/1428428}, author = {BRAGIN, A and Jandó, Gábor and Nádasdy, Zoltán and HETKE, J and WISE, K and Buzsáki, György}, doi = {10.1523/jneurosci.15-01-00047.1995}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {15}, unique-id = {1428428}, issn = {0270-6474}, abstract = {The cellular generation and spatial distribution of gamma frequency (40-100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves, Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path, The frequency changes of gamma and theta waves positively correlated (40-100 Hz and 5-10 Hz, respectively), Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus, Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25-50 Hz) emerged in the CA3-CA1 network, We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.}, keywords = {BEHAVIOR; CELLS; NEURONS; hippocampus; EEG; FIELD POTENTIALS; Theta; THETA-RHYTHM; FREELY-MOVING RATS; dentate gyrus; SYNCHRONIZATION; CAT VISUAL-CORTEX; SOURCE DENSITY ANALYSIS; HILAR REGION; 40 HZ; GAMMA OSCILLATION; UNIT ACTIVITY}, year = {1995}, eissn = {1529-2401}, pages = {47-60}, orcid-numbers = {Nádasdy, Zoltán/0000-0002-6515-9683} }