A Causal Role for Brain-Derived Neurotrophic Factor in the Homeostatic Regulation of Sleep
Open accessAbstract
Slow-wave activity (SWA), the EEG power between 0.5 and 4 Hz during non-rapid eye movement (NREM) sleep, is one of the best characterized markers of sleep need, because it increases as a function of preceding waking duration and decreases during sleep, but the underlying mechanisms remain unknown. We hypothesized that SWA is high at sleep onset because it reflects the occurrence, during the previous waking period, of widespread synaptic potentiation in cortical and subcortical areas. Consistent with this hypothesis, we recently showed that the more rats explore, the stronger is the cortical expression of BDNF during wakefulness, and the larger is the increase in SWA during the subsequent sleep period. There is compelling evidence that BDNF plays a causal role in synaptic potentiation, and exogenous application of BDNF in vivo is sufficient to induce long-term increases in synaptic strength. We therefore performed cortical unilateral microinjections of BDNF in awake rats and measured SWA during the subsequent sleep period. SWA during NREM sleep was higher in the injected hemisphere relative to the contralateral one. The effect was reversible within 2 h, and did not occur during wakefulness or rapid eye movement sleep. Asymmetries in NREM SWA did not occur after vehicle injections. Furthermore, microinjections, during wakefulness, of a polyclonal anti-BDNF antibody or K252a, an inhibitor of BDNF TrkB receptors, led to a local SWA decrease during the following sleep period. These effects were also reversible and specific for NREM sleep. These results show a causal link between BDNF expression during wakefulness and subsequent sleep regulation.
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Procedures assumed to induce local net increases in synaptic potentiation (e.g., the cortical application of BDNF and KCl) induced cortical spreading depression and increased SWA during subsequent sleep, whereas BDNF receptor inhibition decreased SWA.
“Procedures assumed to induce local net increases in synaptic potentiation (e.g., the cortical application of BDNF and KCl) induced cortical spreading depression (81) and increased SWA during subsequent sleep, whereas BDNF receptor inhibition decreased SWA (366,367).”
From About Sleep's Role in Memory (2013) · cites this paper as [367]
The Abstract reports that cortical BDNF injections in awake rats increased local SWA during subsequent NREM sleep, while the K252a injections section reports reduced SWA after blocking the BDNF receptor TrkB. The cited paper does not establish the claim about KCl application. Cortical spreading depression is attached to citation (81) in the citing sentence, not to this source. (LLM, conf=0.86)
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Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Two-Process Model of Sleep Regulation
Binder, M. D., Hirokawa, N., & Windhorst, U. (2008) · Springer eBooks · doi:10.1007/978-3-540-29678-2_6166 · Cited by 3,895 · see citing works
Huber, R., Felice Ghilardi, M., Massimini, M., & Tononi, G. (2004) · Nature · doi:10.1038/nature02663 · Cited by 1,854 · see citing works
Self-citationHippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
Korte, M., Carroll, P., Wolf, E., Brem, G., Thoenen, H., & Bonhoeffer, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8856 · Cited by 1,426 · see citing works
Long-Lasting Neurotrophin-Induced Enhancement of Synaptic Transmission in the Adult Hippocampus
Kang, H., & Schuman, E. M. (1995) · Science · doi:10.1126/science.7886457 · Cited by 1,354 · see citing works
Natural waking and sleep states: a view from inside neocortical neurons
Steriade, M., Timofeev, I., & Grenier, F. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.85.5.1969 · Cited by 1,296 · see citing works
Patterson, S. L., Abel, T., Deuel, T. A. S., Martin, K. C., Rose, J. C., & Kandel, E. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80140-3 · Cited by 1,233 · see citing works
Figurov, A., Pozzo-Miller, L. D., Olafsson, P., Wang, T., & Lu, B. (1996) · Nature · doi:10.1038/381706a0 · Cited by 1,106 · see citing works
BDNF and Activity-Dependent Synaptic Modulation: Figure 1.
Lu, B. (2003) · Learning & Memory · doi:10.1101/lm.54603 · Cited by 945 · see citing works
Ying, S.-W., Futter, M., Rosenblum, K., Webber, M. J., Hunt, S. P., Bliss, T. V. P., & Bramham, C. R. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01532.2002 · Cited by 784 · see citing works
Rapid and selective induction of BDNF expression in the hippocampus during contextual learning
Hall, J., Thomas, K. L., & Everitt, B. (2000) · Nature Neuroscience · doi:10.1038/75698 · Cited by 669 · see citing works
Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity
Huber, R., Ghilardi, M. F., Massimini, M., Ferrarelli, F., Riedner, B. A., Peterson, M. J., & Tononi, G. (2006) · Nature Neuroscience · doi:10.1038/nn1758 · Cited by 579 · see citing works
Self-citationFrom waking to sleeping: neuronal and chemical substrates
Jones, B. E. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.09.009 · Cited by 577 · see citing works
Patterson, S. L., Grover, L. M., Schwartzkroin, P. A., & Bothwell, M. (1992) · Neuron · doi:10.1016/0896-6273(92)90067-n · Cited by 555 · see citing works
Sale, A., Maya Vetencourt, J. F., Medini, P., Cenni, M. C., Baroncelli, L., De Pasquale, R., & Maffei, L. (2007) · Nature Neuroscience · doi:10.1038/nn1899 · Cited by 492 · see citing works
BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia
Baker‐Herman, T. L., Fuller, D. D., Bavis, R. W., Zabka, A. G., Golder, F. J., Doperalski, N. J., Johnson, R. A., Watters, J. J., & Mitchell, G. S. (2003) · Nature Neuroscience · doi:10.1038/nn1166 · Cited by 484 · see citing works
Messaoudi, E., Kanhema, T., Soule, J. D., Tiron, A., Dagytė, G., da Silva, B., & Bramham, C. R. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2883-07.2007 · Cited by 452 · see citing works
Bałkowiec, A., & Katz, D. M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-23-10399.2002 · Cited by 405 · see citing works
Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans
KATTLER, H., DIJK, D., & BORBÉLY, A. A. (1994) · Journal of Sleep Research · doi:10.1111/j.1365-2869.1994.tb00123.x · Cited by 401 · see citing works
Cirelli, C., & Tononi, G. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09187.2000 · Cited by 369 · see citing works
Self-citationMathematical models of sleep regulation
Achermann, P. (2003) · Frontiers in Bioscience · doi:10.2741/1064 · Cited by 358 · see citing works
Rex, C. S., Lin, C.-Y., Kramár, E. A., Chen, L. Y., Gall, C. M., & Lynch, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4037-06.2007 · Cited by 324 · see citing works
Esser, S. K., Hill, S. L., & Tononi, G. (2007) · Sleep · doi:10.1093/sleep/30.12.1617 · Cited by 315 · see citing works
Self-citationKnipper, M., da Penha Berzaghi, M., Blöchl, A., Breer, H., Thoenen, H., & Lindholm, D. (1994) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1994.tb00312.x · Cited by 298 · see citing works
Messaoudi, E., Ying, S., Kanhema, T., Croll, S. D., & Bramham, C. R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-17-07453.2002 · Cited by 297 · see citing works
Brain-Derived Neurotrophic Factor Enhances Long-Term Potentiation in Rat Visual Cortex
Akaneya, Y., Tsumoto, T., Kinoshita, S., & Hatanaka, H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-17-06707.1997 · Cited by 284 · see citing works
Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications
Nagappan, G., & Lu, B. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.07.003 · Cited by 265 · see citing works
Neurotrophins and activity-dependent plasticity
Thoenen, H. (2000) · Progress in brain research · doi:10.1016/s0079-6123(00)28016-3 · Cited by 256 · see citing works
Aicardi, G., Argilli, E., Cappello, S., Santi, S., Riccio, M., Thoenen, H., & Canossa, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406960101 · Cited by 246 · see citing works
Relative Contribution of Endogenous Neurotrophins in Hippocampal Long-Term Potentiation
Chen, G., Kolbeck, R., Barde, Y., Bonhoeffer, T., & Kossel, A. H. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-18-07983.1999 · Cited by 244 · see citing works
Huber, R., Esser, S. K., Ferrarelli, F., Massimini, M., Peterson, M. J., & Tononi, G. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000276 · Cited by 232 · see citing works
Self-citationExploratory Behavior, Cortical BDNF Expression, and Sleep Homeostasis
Huber, R., Tononi, G., & Cirelli, C. (2007) · Sleep · doi:10.1093/sleep/30.2.129 · Cited by 224 · see citing works
Self-citationDisconnection of intracortical synaptic linkages disrupts synchronization of a slow oscillation
Amzica, F., & Steriade, M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-06-04658.1995 · Cited by 221 · see citing works
Messaoudi, E., Bårdsen, K., Srebro, B., & Bramham, C. R. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.1.496 · Cited by 208 · see citing works
Vyazovskiy, V., Borbély, A. A., & Tobler, I. (2000) · Journal of Sleep Research · doi:10.1046/j.1365-2869.2000.00230.x · Cited by 203 · see citing works
Self-citationWardle, R. A., & Poo, M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08722.2003 · Cited by 201 · see citing works
Klintsova, A. Y., Dickson, E., Yoshida, R., & Greenough, W. T. (2004) · Brain Research · doi:10.1016/j.brainres.2004.09.003 · Cited by 200 · see citing works
Gärtner, A., & Staiger, V. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092129699 · Cited by 195 · see citing works
Tobler, I. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-6645-3.00009-8 · Cited by 161 · see citing works
Brain-derived neurotrophic factor is an anterograde survival factor in the rat visual system
Caleo, M., Menna, E., Chierzi, S., Cenni, M. C., & Maffei, L. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00713-2 · Cited by 122 · see citing works
Sala, R., Viegi, A., Rossi, F., Pizzorusso, T., Bonanno, G., Raiteri, M., & Maffei, L. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00227.x · Cited by 120 · see citing works
Martı́nez-González, D., Lesku, J. A., & Rattenborg, N. C. (2008) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2008.00636.x · Cited by 105 · see citing works
Sleep-Dependent Plasticity Requires Cortical Activity
Jha, S. K., Jones, B. E., Coleman, T., Steinmetz, N., Law, C.-T., Griffin, G., Hawk, J., Dabbish, N., Kalatsky, V. A., & Frank, M. G. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2722-05.2005 · Cited by 96 · see citing works
A caged Ab reveals an immediate/instructive effect of BDNF during hippocampal synaptic potentiation
Kossel, A. H., Cambridge, S. B., Wagner, U., & Bonhoeffer, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251326998 · Cited by 96 · see citing works
Brain-derived neurotrophic factor enhances spontaneous sleep in rats and rabbits
Kushikata, T., Fang, J., & Krueger, J. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1334 · Cited by 95 · see citing works
Gooney, M., & Lynch, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00334.x · Cited by 80 · see citing works
Hairston, I. S., Peyron, C., Denning, D. P., Ruby, N. F., Flores, J., Sapolsky, R. M., Heller, H. C., & O’Hara, B. F. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00894.2003 · Cited by 79 · see citing works
Tobler, I. (2005) · Elsevier eBooks · doi:10.1016/b0-72-160797-7/50014-8 · Cited by 74 · see citing works
Jiang, B., Akaneya, Y., Hata, Y., & Tsumoto, T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03761.2003 · Cited by 60 · see citing works
Vyazovskiy, V. V., Welker, E., Fritschy, J., & Tobler, I. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03583.x · Cited by 58 · see citing works
Self-citationIn vivo insular cortex LTP induced by brain-derived neurotrophic factor
Escobar, M. L., Figueroa-Guzmán, Y., & Gómez-Palacio-Schjetnan, A. (2003) · Brain Research · doi:10.1016/j.brainres.2003.08.015 · Cited by 58 · see citing works
Wigren, H., Schepens, M. A. A., Matto, V., Stenberg, D., & Porkka‐Heiskanen, T. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.04.046 · Cited by 54 · see citing works
Tobler, I., Franken, P., Gao, B., Jaggi, K., & Borbély, A. A. (1994) · PubMed · Cited by 32 · see citing works
Naimark, A., Barkai, E., Matar, M. A., et al. (2007) · Neural Plasticity · doi:10.1155/2007/13427 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rasch, B., & Born, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00032.2012 · Cited by 2,783 · see citing works
“SWS is hallmarked by slow high-amplitude EEG oscillations (slow wave activity, SWA), whereas REM sleep (also termed paradoxical sleep) is Physiol Rev 93: 681–766, 2013 doi:10.1152/physrev.00032.2012 6810031-9333/13 Copyright © 2013 the American Physiological Society by 10.220.32.247 on O ctober 25, 2016 http://physrev…”
BackgroundInfluentialTononi, G., & Cirelli, C. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.025 · Cited by 2,356 · see citing works
Self-citationControl of sleep and wakefulness
Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00032.2011 · Cited by 1,477 · see citing works
Cortical firing and sleep homeostasis
Vyazovskiy, V. V., Olcese, U., Lazimy, Y. M., Faraguna, U., Esser, S. K., Williams, J. C., Cirelli, C., & Tononi, G. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.024 · Cited by 740 · see citing works
Self-citationThe Role of Cytokines in Sleep Regulation
Krueger, J. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208786549281 · Cited by 507 · see citing works
Kurth, S., Ringli, M., Geiger, A., LeBourgeois, M., Jenni, O. G., & Huber, R. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.2532-10.2010 · Cited by 373 · see citing works
EEG sleep slow-wave activity as a mirror of cortical maturation
Buchmann, A., Ringli, M., Kurth, S., Schaerer, M., Geiger, A., Jenni, O. G., & Huber, R. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq129 · Cited by 273 · see citing works
Salvadore, G., Cornwell, B. R., Colon-Rosario, V., Coppola, R., Grillon, C., Zarate, C. A., & Manji, H. K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.014 · Cited by 277 · see citing works
Duncan, W. C., Sarasso, S., Ferrarelli, F., Selter, J., Riedner, B. A., Hejazi, N. S., Yuan, P., Brutsche, N., Manji, H. K., Tononi, G., et al. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000545 · Cited by 256 · see citing works
Self-citationMechanisms of sleep-dependent consolidation of cortical plasticity
Aton, S. J., Seibt, J., Dumoulin, M., Jha, S. K., Steinmetz, N., Coleman, T., Naidoo, N., & Frank, M. G. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.007 · Cited by 244 · see citing works
Machado-Vieira, R., Manji, H. K., & Zarate, C. A. (2009) · The Neuroscientist · doi:10.1177/1073858409336093 · Cited by 171 · see citing works
Sleep homeostasis in the rat is preserved during chronic sleep restriction
Leemburg, S., Vyazovskiy, V. V., Olcese, U., Bassetti, C. L., Tononi, G., & Cirelli, C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002570107 · Cited by 154 · see citing works
Self-citationSleep, circadian biology and skeletal muscle interactions: Implications for metabolic health
Morrison, M., Halson, S. L., Weakley, J., & Hawley, J. A. (2022) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2022.101700 · Cited by 118 · see citing works
Alkire, M. T., Asher, C. D., Franciscus, A. M., & Hahn, E. L. (2009) · Anesthesiology · doi:10.1097/aln.0b013e31819c461c · Cited by 105 · see citing works
Ketamine, Sleep, and Depression: Current Status and New Questions
Duncan, W. C., & Zarate, C. A. (2013) · Current Psychiatry Reports · doi:10.1007/s11920-013-0394-z · Cited by 76 · see citing works
Genetic determination of sleep EEG profiles in healthy humans
Landolt, H.-P. (2011) · Progress in Brain Research · doi:10.1016/b978-0-444-53839-0.00004-1 · Cited by 67 · see citing works
Neuroscience-driven discovery and development of sleep therapeutics
Dresler, M., Spoormaker, V. I., Beitinger, P., Czisch, M., Kimura, M., Steiger, A., & Holsboer, F. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.012 · Cited by 63 · see citing works
Duncan, W. C., Ballard, E. D., & Zarate, C. A. (2017) · Handbook of Experimental Pharmacology · doi:10.1007/164_2017_51 · Cited by 58 · see citing works
Li, X., Liang, S., Li, Z., Li, S., Xia, M., Verkhratsky, A., & Li, B. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00734 · Cited by 54 · see citing works
Faraguna, U., Nelson, A., Vyazovskiy, V. V., Cirelli, C., & Tononi, G. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhq041 · Cited by 54 · see citing works
Self-citationMikoteit, T., Brand, S., Eckert, A., Holsboer-Trachsler, E., & Beck, J. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.12.020 · Cited by 39 · see citing works
- Authors
- Faraguna, U., Vyazovskiy, V. V., Nelson, A. B., Tononi, G., & Cirelli, C.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-04-09
- Volume
- 28
- Issue
- 15
- Pages
- 4088-4095
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2597531
- OpenAlex
- W2013825587
- Cited by
- 300
- References
- 54
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 20 · 2023: 18 · 2022: 16 · 2021: 18 · 2020: 21 · 2019: 18 · 2018: 10 · 2017: 11 · 2016: 21 · 2015: 17 · 2014: 19 · 2013: 26 · 2012: 20
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- National Institutes of Health (5p20mh077967-04)
- National Institute of Mental Health (P20MH-077967)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- brain-derived neurotrophic factor, slow-wave activity, NREM sleep, sleep homeostasis, synaptic potentiation, TrkB receptor, K252a, sleep need, wakefulness, rats
- MeSH terms
- Animals, Antibodies, Carbazoles, Electroencephalography, Frontal Lobe, Homeostasis, Injections, Male, Microinjections, Rats, Inbred WKY, Sleep, Time Factors, Brain-Derived Neurotrophic Factor, Receptor, trkB, Indole Alkaloids, Rats
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