TY - JOUR AU - Kalweit, Alexander Nikolai AU - Yang, Honghong AU - Colitti-Klausnitzer, Jens AU - Fülöp, Lívia AU - Bozsó, Zsolt AU - Penke, Botond AU - Manahan-Vaughan, Denise TI - Acute intracerebral treatment with amyloid-beta (1-42) alters the profile of neuronal oscillations that accompany LTP induction and results in impaired LTP in freely behaving rats JF - FRONTIERS IN BEHAVIORAL NEUROSCIENCE J2 - FRONT BEHAV NEUROSCI VL - 9 PY - 2015 PG - 16 SN - 1662-5153 DO - 10.3389/fnbeh.2015.00103 UR - https://m2.mtmt.hu/api/publication/2940235 ID - 2940235 LA - English DB - MTMT ER - TY - JOUR AU - Varga, Edina AU - Juhász, Gábor AU - Bozsó, Zsolt AU - Penke, Botond AU - Fülöp, Lívia AU - Szegedi, Viktor TI - Amyloid-β1-42 disrupts synaptic plasticity by altering glutamate recycling at the synapse JF - JOURNAL OF ALZHEIMER'S DISEASE J2 - J ALZHEIMERS DIS VL - 45 PY - 2015 IS - 2 SP - 449 EP - 456 PG - 8 SN - 1387-2877 DO - 10.3233/JAD-142367 UR - https://m2.mtmt.hu/api/publication/2812783 ID - 2812783 AB - Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-beta peptide (Abeta) and neurofibrillary tangles. Evidence has been reported that Abeta1-42 plays an essential pathogenic role in decreased spine density, impairment of synaptic plasticity, and neuronal loss with disruption of memory-related synapse function, all associated with AD. Experimentally, Abeta1-42 oligomers perturb hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory. Abeta was also reported to perturb synaptic glutamate (Glu)-recycling by inhibiting excitatory-amino-acid-transporters. Elevated level of extracellular Glu leads to activation of perisynaptic receptors, including NR2B subunit containing NMDARs. These receptors were shown to induce impaired LTP and enhanced long-term depression and proapoptotic pathways, all central features of AD. In the present study, we investigated the role of Glu-recycling on Abeta1-42-induced LTP deficit in the CA1. We found that Abeta-induced LTP damage, which was mimicked by the Glu-reuptake inhibitor TBOA, could be rescued by blocking the NR2B subunit of NMDA receptors. Furthermore, decreasing the level of extracellular Glu using a Glu scavenger also restores TBOA or Abeta induces LTP damage. Overall, these results suggest that reducing ambient Glu in the brain can be protective against Abeta-induced synaptic disruption. LA - English DB - MTMT ER - 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 - Verret, L AU - Mann, EO AU - Hang, GB AU - Barth, Albert AU - Cobos, I AU - Ho, K AU - Devidze, N AU - Masliah, E AU - Kreitzer, AC AU - Mody, I AU - Mucke, L AU - Palop, JJ TI - Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. JF - CELL J2 - CELL VL - 149 PY - 2012 IS - 3 SP - 708 EP - 721 PG - 14 SN - 0092-8674 DO - 10.1016/j.cell.2012.02.046 UR - https://m2.mtmt.hu/api/publication/3050948 ID - 3050948 N1 - Gladstone Institute of Neurological Disease, San Francisco, CA 94158, United States Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, United States Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158, United States Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, United States Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, United States Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, United States Cited By :784 Export Date: 12 March 2024 CODEN: CELLB Correspondence Address: Palop, J.J.; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, United States; email: jpalop@gladstone.ucsf.edu Chemicals/CAS: parvalbumin, 56094-12-3, 83667-75-8 Funding details: National Institutes of Health, NIH, AG011385, AG022074, AG18440, AG5131, NS002808, NS065780 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R01NS030549 Funding details: National Center for Research Resources, NCRR Funding details: McKnight Foundation Funding text 1: This work was supported by a Stephen D. Bechtel, Jr. Foundation Young Investigator Award to J.J.P.; National Institutes of Health Grants AG022074, AG011385, and NS065780 to L.M. and NS002808, NS030549, AG5131, and AG18440 to E.M.; the Philippe Foundation Award to L.V.; the Coelho Endowment to I.M.; Pew and McKnight Foundations to A.C.K.; Epilepsy Foundation Postdoctoral Fellowship to E.O.M.; and facilities grants from Stephen D. Bechtel, Jr. and the National Center for Research Resources. We thank A. Escayg for the Nav1.1-BAC transgenic mice; J. Noebels and A. Gittis for helpful comments; G.Q. Yu, X. Wang, W. Guo, E. Pham, K. Bummer, I. Lo, and D.H. Kim for excellent technical support; and G. Howard and S. Ordway for editorial review. AB - Alzheimer's disease (AD) results in cognitive decline and altered network activity, but the mechanisms are unknown. We studied human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Electroencephalographic recordings in hAPP mice revealed spontaneous epileptiform discharges, indicating network hypersynchrony, primarily during reduced gamma oscillatory activity. Because this oscillatory rhythm is generated by inhibitory parvalbumin (PV) cells, network dysfunction in hAPP mice might arise from impaired PV cells. Supporting this hypothesis, hAPP mice and AD patients had decreased levels of the interneuron-specific and PV cell-predominant voltage-gated sodium channel subunit Nav1.1. Restoring Nav1.1 levels in hAPP mice by Nav1.1-BAC expression increased inhibitory synaptic activity and gamma oscillations and reduced hypersynchrony, memory deficits, and premature mortality. We conclude that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD. 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 - Klausberger, T AU - Somogyi, Péter Pál TI - Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. JF - SCIENCE J2 - SCIENCE VL - 321 PY - 2008 IS - 5885 SP - 53 EP - 57 PG - 5 SN - 0036-8075 DO - 10.1126/science.1149381 UR - https://m2.mtmt.hu/api/publication/2086363 ID - 2086363 N1 - Megjegyzés-27028849 Megjegyzés-10324201 [273006] Megjegyzés-21921752 Z9: 231 WC: Multidisciplinary Sciences Cited By :1085 Export Date: 21 August 2019 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1106 Export Date: 14 November 2019 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1133 Export Date: 6 March 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1133 Export Date: 12 March 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1140 Export Date: 15 April 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1158 Export Date: 18 May 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1161 Export Date: 20 May 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1162 Export Date: 23 May 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1162 Export Date: 24 May 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1162 Export Date: 25 May 2020 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1235 Export Date: 18 March 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1235 Export Date: 23 March 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1239 Export Date: 31 March 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1239 Export Date: 6 April 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1239 Export Date: 7 April 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1241 Export Date: 13 April 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1241 Export Date: 14 April 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1244 Export Date: 20 April 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1244 Export Date: 26 April 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 Cited By :1283 Export Date: 7 September 2021 CODEN: SCIEA Correspondence Address: Klausberger, T.; MRC Anatomical Neuropharmacology Unit, , Oxford OX1 3TH, United Kingdom; email: thomas.klausberger@pharm.ox.ac.uk Chemicals/CAS: gamma-Aminobutyric Acid, 56-12-2 AB - In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (gamma- aminobutyric acid-releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain- specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior. LA - English DB - MTMT ER - TY - JOUR AU - Klausberger, T AU - Magill, PJ AU - Marton, LF AU - Roberts, JD AU - Cobden, PM AU - Buzsáki, György AU - Somogyi, Péter Pál TI - Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. JF - NATURE J2 - NATURE VL - 421 PY - 2003 IS - 6925 SP - 844 EP - 848 PG - 5 SN - 0028-0836 DO - 10.1038/nature01374 UR - https://m2.mtmt.hu/api/publication/2138091 ID - 2138091 AB - Neural-network oscillations at distinct frequencies have been implicated in the encoding, consolidation and retrieval of information in the hippocampus. Some GABA (gamma-aminobutyric acid)-containing interneurons fire phase-locked to theta oscillations (4-8 Hz) or to sharp-wave-associated ripple oscillations (120-200 Hz), which represent different behavioural states. Interneurons also entrain pyramidal cells in vitro. The large diversity of interneurons poses the question of whether they have specific roles in shaping distinct network activities in vivo. Here we report that three distinct interneuron types--basket, axo-axonic and oriens-lacunosum-moleculare cells--visualized and defined by synaptic connectivity as well as by neurochemical markers, contribute differentially to theta and ripple oscillations in anaesthetized rats. The firing patterns of individual cells of the same class are remarkably stereotyped and provide unique signatures for each class. We conclude that the diversity of interneurons, innervating distinct domains of pyramidal cells, emerged to coordinate the activity of pyramidal cells in a temporally distinct and brain-state-dependent manner. LA - English DB - MTMT ER -