The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Gamma oscillations in the hippocampus require high complex I gene expression and strong functional performance of mitochondria
Abstract
Fast neuronal network oscillations in the gamma range (~30-90 Hz) have been implicated in complex brain functions such as sensory processing, memory formation and, perhaps, consciousness, and appear to be exceptionally vulnerable to various pathologies. However, both energy demand and mitochondrial performance underlying gamma oscillations are unknown. We investigated the fundamental relationship between acetylcholine-induced gamma oscillations, mitochondrial gene expression and oxidative metabolism in hippocampal slice preparations of mouse and rat by applying electrophysiology, in situ hybridization, quantitative polymerase chain reaction, oxygen sensor microelectrode (interstitial partial oxygen pressure) and imaging of mitochondrial redox state [nicotinamide adenine dinucleotide (phosphate) and flavin adenine dinucleotide fluorescence]. We show that (i) gamma oscillation power, oxygen consumption and expression of complex I (nicotinamide adenine dinucleotide:ubiquinone oxidoreductase) subunits are higher in hippocampal subfield CA3 than in CA1 and dentate gyrus; (ii) the amount of oxygen consumption of gamma oscillations reaches that of seizure-like events; (iii) gamma oscillations are exquisitely sensitive to pharmacological complex I inhibition; and (iv) gamma oscillations utilize mitochondrial oxidative capacity near limit. These data suggest that gamma oscillations are especially energy demanding and require both high complex I expression and strong functional performance of mitochondria. Our study helps to explain the exceptional vulnerability of complex brain functions in ischaemia as well as in neurodegenerative and psychiatric disorders that are associated with mitochondrial dysfunction.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The large amounts of ATP needed to sustain gamma oscillations are supplied by a high density of mitochondria [81][82][83].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [83]
In the citing paper
“Studies have shown that the rate of oxygen consumption during hippocampal gamma oscillations can be equivalent to the rate of oxygen spent during a seizure [83,84].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [83]
Citations
Cites
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
Driving fast-spiking cells induces gamma rhythm and controls sensory responses
Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L.-H., & Moore, C. I. (2009) · Nature · doi:10.1038/nature08002 · Cited by 2,603
Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks
Bartos, M., Vida, I., & Jonas, P. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2044 · Cited by 2,070
Effect of anoxia on ion distribution in the brain
Hansen, A. J. (1985) · Physiological Reviews · doi:10.1152/physrev.1985.65.1.101 · Cited by 1,342
Mitochondria in neuroplasticity and neurological disorders
Mattson, M. P., Gleichmann, M., & Cheng, A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.010 · Cited by 1,081
Mechanisms of Gamma Oscillations in the Hippocampus of the Behaving Rat
Csicsvari, J., Jamieson, B. G., Wise, K. D., & Buzsáki, G. (2003) · Neuron · doi:10.1016/s0896-6273(02)01169-8 · Cited by 1,031
The neural basis of functional brain imaging signals
Attwell, D., & Iadecola, C. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02264-6 · Cited by 957
Mootha, V. K., Bunkenborg, J., Olsen, J. V., Hjerrild, M., Wisniewski, J. R., Stahl, E., Bolouri, M. S., Ray, H. N., Sihag, S., Kamal, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00926-7 · Cited by 889
Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro
Fisahn, A., Pike, F. G., Buhl, E. H., & Paulsen, O. (1998) · Nature · doi:10.1038/28179 · Cited by 884
Mitochondria and neuronal activity
Kann, O., & Kovács, R. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00222.2006 · Cited by 871
Self-citationHemodynamic Signals Correlate Tightly with Synchronized Gamma Oscillations
Niessing, J., Ebisch, B., Schmidt, K. E., Niessing, M., Singer, W., & Galuske, R. A. W. (2005) · Science · doi:10.1126/science.1110948 · Cited by 806
Two-Photon Fluorescence Spectroscopy and Microscopy of NAD(P)H and Flavoprotein
Huang, S., Heikal, A. A., & Webb, W. W. (2002) · Biophysical Journal · doi:10.1016/s0006-3495(02)75621-x · Cited by 763
Synchronization of neural activity across cortical areas correlates with conscious perception
Melloni, L., Molina, C., Pena, M., Torres, D., Singer, W., & Rodriguez, E. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4623-06.2007 · Cited by 716
Uhlhaas, P. J., Haenschel, C., Nikolic, D., & Singer, W. (2008) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn062 · Cited by 629
Tissue oxygen tension and brain sensitivity to hypoxia
Erecińska, M., & Silver, I. A. (2001) · Respiration Physiology · doi:10.1016/s0034-5687(01)00306-1 · Cited by 615
Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo
Traub, R. D., Whittington, M. A., Colling, S. B., Buzsáki, G., & Jefferys, J. G. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021397 · Cited by 607
Mitochondrial Disorders in the Nervous System
DiMauro, S., & Schon, E. A. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094302 · Cited by 541
Fuchs, E. C., Zivkovic, A. R., Cunningham, M. O., Middleton, S., LeBeau, F. E. N., Bannerman, D. M., Rozov, A., Whittington, M. A., Traub, R. D., Rawlins, J. N. P., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.031 · Cited by 532
Liu, J., Head, E., Gharib, A., Yuan, W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W., & Ames, B. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261709299 · Cited by 504
Cortical spreading depression causes and coincides with tissue hypoxia
Takano, T., Tian, G.-F., Peng, W., Lou, N., Lovatt, D., Hansen, A. J., Kasischke, K. A., & Nedergaard, M. (2007) · Nature Neuroscience · doi:10.1038/nn1902 · Cited by 472
Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance
Montgomery, S. M., & Buzsáki, G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701826104 · Cited by 455
Lack of myostatin results in excessive muscle growth but impaired force generation
Amthor, H., Macharia, R., Navarrete, R., Schuelke, M., Brown, S., Otto, A., Voït, T., Muntoni, F., Vrbovà, G., Partridge, T. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604893104 · Cited by 438
Self-citationWhat causes mitochondrial DNA deletions in human cells?
Krishnan, K. J., Reeve, A. K., Samuels, D. C., Chinnery, P. F., Blackwood, J. K., Taylor, R. W., Wanrooij, S., Spelbrink, J. N., Lightowlers, R. N., & Turnbull, D. M. (2008) · Nature Genetics · doi:10.1038/ng.f.94 · Cited by 376
Mitochondrial uncoupling proteins in the cns: in support of function and survival
Andrews, Z. B., Diano, S., & Horváth, T. L. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1767 · Cited by 374
Maier, N., Nimmrich, V., & Draguhn, A. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.044602 · Cited by 344
Chih, C.-P., & Roberts, E. L. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000081369.51727.6f · Cited by 325
Mann, E. O., Suckling, J. M., Hájos, N., Greenfield, S. A., & Paulsen, O. (2005) · Neuron · doi:10.1016/j.neuron.2004.12.016 · Cited by 324
Hájos, N., Pálhalmi, J., Mann, E. O., Németh, B., Paulsen, O., & Freund, T. F. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2113-04.2004 · Cited by 321
Vermylen, C., Cornu, G., Ferster, A., Brichard, B., Ninane, J., Ferrant, A., Zenebergh, A., Maes, P., Dhooge, C., Benoît, Y., et al. (1998) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1701291 · Cited by 312
Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease
Distelmaier, F., Koopman, W. J. H., van den Heuvel, L. P., Rodenburg, R. J., Mayatepek, E., Willems, P. H. G. M., & Smeitink, J. A. M. (2008) · Brain · doi:10.1093/brain/awp058 · Cited by 310
Simoni, A. D., Griesinger, C. B., & Edwards, F. A. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.039099 · Cited by 289
Mitochondrial complex I: structure, function and pathology
Janssen, R. J. R. J., Nijtmans, L. G., Heuvel, L. P. V. D., & Smeitink, J. A. M. (2006) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-006-0362-4 · Cited by 276
Induction of sharp wave–ripple complexes in vitro and reorganization of hippocampal networks
Behrens, C. J., van den Boom, L. P., de Hoz, L., Friedman, A., & Heinemann, U. (2005) · Nature Neuroscience · doi:10.1038/nn1571 · Cited by 262
Rodriguez, R., Kallenbach, U., Singer, W., & Munk, M. H. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1839-04.2004 · Cited by 246
D’Ambrosio, R., Gordon, D., & Winn, H. R. (2002) · Journal of Neurophysiology · doi:10.1152/jn.00240.2001 · Cited by 235
Maintaining network activity in submerged hippocampal slices: importance of oxygen supply
Hájos, N., Ellender, T. J., Zemankovics, R., Mann, E. O., Exley, R. A., Cragg, S. J., Freund, T. F., & Paulsen, O. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06577.x · Cited by 229
Hippocampal Gamma Oscillations Increase with Memory Load
van Vugt, M. K., Schulze‐Bonhage, A., Litt, B., Brandt, A., & Kahana, M. J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0567-09.2010 · Cited by 226
Mann, E. O., & Mody, I. (2010) · Nature Neuroscience · doi:10.1038/nn.2464 · Cited by 222
Mitochondrial DNA modifies cognition in interaction with the nuclear genome and age in mice
Roubertoux, P. L., Sluyter, F., Carlier, M., Marcet, B., Maarouf-Veray, F., Chérif, C., Marican, C., Arecchi, P., Godin, F., Jamon, M., et al. (2003) · Nature Genetics · doi:10.1038/ng1230 · Cited by 205
Axmacher, N., Schmitz, D. P., Wagner, T., Elger, C. E., & Fell, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1778-08.2008 · Cited by 204
Kasahara, T., Kubota, M., Miyauchi, T., Noda, Y., Mouri, A., Nabeshima, T., & Kato, T. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001824 · Cited by 178
Oxidative and Nonoxidative Metabolism of Excited Neurons and Astrocytes
GJEDDE, A. H., Marrett, S., & Vafaee, M. S. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200201000-00001 · Cited by 168
Oxidation–reduction states of NADH in vivo: From animals to clinical use
Mayevsky, A., & Chance, B. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.05.001 · Cited by 159
Offenhauser, N., Thomsen, K., Caesar, K., & Lauritzen, M. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.082776 · Cited by 145
Kann, O., Kovács, R., Njunting, M., Behrens, C. J., Otáhal, J., Lehmann, T., Gabriel, S., & Heinemann, U. (2005) · Brain · doi:10.1093/brain/awh568 · Cited by 143
Self-citationPopulations of hippocampal inhibitory neurons express different levels of cytochrome c
Gulyás, A. I., Buzsáki, G., Freund, T. F., & Hirase, H. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04814.x · Cited by 142
Huchzermeyer, C., Albus, K., Gabriel, H.-J., Otáhal, J., Taubenberger, N., Heinemann, U., Kovács, R., & Kann, O. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4105-07.2008 · Cited by 117
Self-citationKronenberg, G., Harms, C., Sobol, R. W., Cardozo‐Pelaez, F., Linhart, H., Winter, B., Balkaya, M., Gertz, K. R., Gay, S. B., Cox, D., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0940-08.2008 · Cited by 111
Synaptic reorganization in explanted cultures of rat hippocampus
Gutiérrez, R., & Heinemann, U. (1999) · Brain Research · doi:10.1016/s0006-8993(98)01101-9 · Cited by 103
Kovács, R., Kardos, J., Heinemann, U., & Kann, O. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4000-04.2005 · Cited by 101
Self-citationKann, O., Schuchmann, S., Buchheim, K., & Heinemann, U. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00026-5 · Cited by 98
Self-citationBrennan, A. M., Connor, J. A., & Shuttleworth, C. W. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600292 · Cited by 97
Fast network oscillations induced by potassium transients in the rat hippocampus in vitro
LeBeau, F. E. N., Towers, S. K., Traub, R. D., Whittington, M. A., & Buhl, E. H. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.015933 · Cited by 96
Effects of membrane depolarization on nicotinamide nucleotide fluorescence in brain slices
Lipton, P. (1973) · Biochemical Journal · doi:10.1042/bj1360999 · Cited by 78
Verweij, B. H., Amelink, G. J., & Muizelaar, J. P. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)61008-x · Cited by 77
Schuchmann, S., Kovacs, R., Kann, O., Heinemann, U., & Buchheim, K. (2001) · Brain Research Protocols · doi:10.1016/s1385-299x(01)00080-0 · Cited by 75
Self-citationHeinemann, U., Schaible, H., & Schmidt, R. F. (1990) · Experimental Brain Research · doi:10.1007/bf00608237 · Cited by 67
Gerich, F. J., Hepp, S., Probst, I., & Müller, M. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01015.2005 · Cited by 65
Muscarinic blockade weakens interaction of gamma with theta rhythms in mouse hippocampus
Hentschke, H., Perkins, M. G., Pearce, R. A., & Banks, M. I. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05779.x · Cited by 63
Dendritic development of dentate granule cells in the absence of their specific extrinsic afferents
Zafirov, S., Heimrich, B., & Frotscher, M. (1994) · The Journal of Comparative Neurology · doi:10.1002/cne.903450312 · Cited by 55
Wójtowicz, A. M., van den Boom, L., Chakrabarty, A., Maggio, N., Haq, R. U., Behrens, C., & Heinemann, U. (2009) · Hippocampus · doi:10.1002/hipo.20508 · Cited by 53
Complex I and energy thresholds in the brain
Pathak, R. U., & Davey, G. P. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.05.443 · Cited by 51
Masamoto, K., Omura, T., Takizawa, N., Kobayashi, H., Katura, T., Maki, A., Kawaguchi, H., & Tanishita, K. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000084248.20114.b3 · Cited by 45
Falk-Krzesinski, H. J., & Wolfe, A. J. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.5.1174-1184.1998 · Cited by 44
Zickermann, V., Dröse, S., Tocilescu, M. A., Zwicker, K., Kerscher, S., & Brandt, U. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9171-9 · Cited by 41
Oxygen insufficiency during hypoxic hypoxia in rat brain cortex
LaManna, J. C., Light, A. I., Peretsman, S. J., & Rosenthal, M. (1984) · Brain Research · doi:10.1016/0006-8993(84)91238-1 · Cited by 37
Cited by
Sorted by citations
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124
Kann, O., Papageorgiou, I. E., & Draguhn, A. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.104 · Cited by 295
Self-citationThe interneuron energy hypothesis: Implications for brain disease
Kann, O. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.08.005 · Cited by 270
Self-citationSteullet, P., Cabungcal, J. H., Monin, A., Dwir, D., O'Donnell, P., Cuenod, M., & Do, K. Q. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2014.06.021 · Cited by 262
Mitochondrial Dysfunction in Parkinson’s Disease—Cause or Consequence?
Chen, C., Turnbull, D. M., & Reeve, A. K. (2019) · Biology · doi:10.3390/biology8020038 · Cited by 260
Metadata
- Authors
- Kann, O., Huchzermeyer, C., Kovács, R., Wirtz, S., & Schuelke, M.
- Affiliations
- Heidelberg University (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Stiftung Charité (DE)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12-22
- Volume
- 134
- Issue
- 2
- Pages
- 345-358
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2100518016
- Cited by
- 189
- References
- 67
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 8 · 2023: 13 · 2022: 15 · 2021: 13 · 2020: 14 · 2019: 15 · 2018: 10 · 2017: 9 · 2016: 15 · 2015: 14 · 2014: 14 · 2013: 7 · 2012: 11
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gamma oscillations, hippocampus, complex I, mitochondrial gene expression, mitochondrial oxidative metabolism, oxygen consumption, acetylcholine, CA3, mitochondrial redox state, mitochondrial complex I inhibition, energy demand, seizure-like events, mitochondrial dysfunction
- MeSH terms
- Acetylcholine, Animals, Hippocampus, Mice, Inbred C57BL, Mitochondria, Oxidation-Reduction, Oxygen Consumption, Gene Expression, Rats, Wistar, Electron Transport Complex I, Mice, Rats, Brain Waves, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
