Stimulation on the Positive Phase of Hippocampal Theta Rhythm Induces Long-Term Potentiation That Can Be Depotentiated by Stimulation on the Negative Phase in Area CA1 In Vivo
Open accessAbstract
Long-term potentiation (LTP) of synaptic transmission induced by high-frequency stimulation (HFS) is considered to be a model for learning processes; however, standard HFS protocols consisting of long trains of HFS are very different from the patterns of spike firing in freely behaving animals. We have investigated the ability of brief bursts of HFS triggered at different phases of background theta rhythm to mimic more natural activity patterns. We show that a single burst of five pulses at 200 Hz given on the positive phase of tail pinch-triggered theta rhythm reliably induced LTP in the stratum radiatum of the hippocampus of urethane-anesthetized rats. Three of these bursts saturated LTP, and 10 bursts occluded the induction of LTP by long trains of HFS. Burst stimulation on the negative phase or at zero phase of theta did not induce LTP or long-term depression. In addition, stimulation with 10 bursts on the negative phase of theta reversed previously established LTP. The results show that the phase of sensory-evoked theta rhythm powerfully regulates the ability of brief HFS bursts to elicit either LTP or depotentiation of synaptic transmission. Furthermore, because complex spike activity of approximately five pulses on the positive phase of theta rhythm can be observed in freely moving rats, LTP induced by the present theta-triggered stimulation protocol might model putative synaptic plastic changes during learning more closely than standard HFS-induced LTP.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Burst stimulation of CA1 inputs can induce LTP or LTD depending on whether it arrives at the peak or trough, respectively, of ongoing theta oscillations.
“Burst stimulation of CA1 inputs can induce LTP or LTD depending on whether it arrives at the peak or trough, respectively, of ongoing theta oscillations (561, 892).”
From About Sleep's Role in Memory (2013) · cites this paper as [561]
The Results section reports that bursts on the positive phase induced LTP, but bursts on the negative phase did not induce LTD. Negative-phase bursts instead depotentiated previously induced LTP; the Discussion explicitly says LTD was not observed in this study. The copy provides no page numbers for these passages. (LLM, conf=0.92)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Huang, Y.-Y., Kandel, E. R., Varshavsky, L., Brandont, E. P., Qi, M., Idzerda, R. L., Stanley McKnight, G., & Bourtchouladz, R. (1995) · Cell · doi:10.1016/0092-8674(95)90146-9 · Cited by 267 · see citing works
Normal spatial learning despite regional inhibition of LTP in mice lacking Thy-1
Nosten-Bertrand, M., Errington, M. L., Murphy, K. P. S. J., Tokugawa, Y., Barboni, E., Kozlova, E., Michalovich, D., Morris, R. G. M., Silver, J., Stewart, C. L., et al. (1996) · Nature · doi:10.1038/379826a0 · Cited by 232 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Ho ¨lscher C, Anwyl R, Rowan M (1997c) Block of theta-burst induced LTP by 1S,3S-ACPD: f urther evidence against LTP as a model for learning. Neuroscience, in press.
Cited by
Sorted by citations
Diekelmann, S., & Born, J. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2762 · Cited by 3,760 · see citing works
Theta oscillations in the hippocampus
Buzsáki, G. (2002) · Neuron · doi:10.1016/s0896-6273(02)00586-x · Cited by 3,332 · see citing works
Rasch, B., & Born, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00032.2012 · Cited by 2,783 · see citing works
“Burst stimulation of CA1 inputs can induce LTP or LTD depending on whether it arrives at the peak or trough, respectively, of ongoing theta oscillations (561, 892).”
BackgroundTononi, G., & Cirelli, C. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.025 · Cited by 2,356 · see citing works
Sleep-Dependent Learning and Memory Consolidation
Walker, M. P., & Stickgold, R. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.031 · Cited by 1,113 · see citing works
Entrainment of Neocortical Neurons and Gamma Oscillations by the Hippocampal Theta Rhythm
Sirota, A., Montgomery, S., Fujisawa, S., Isomura, Y., Zugaro, M., & Buzsáki, G. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.014 · Cited by 1,015 · see citing works
Hasselmo, M. E., Bodelón, C., & Wyble, B. P. (2002) · Neural Computation · doi:10.1162/089976602317318965 · Cited by 875 · see citing works
Theta and gamma oscillations during encoding predict subsequent recall
Sederberg, P. B., Kahana, M. J., Howard, M. W., Donner, E. J., & Madsen, J. R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10809.2003 · Cited by 750 · see citing works
Sleep, learning, and dreams: off-line memory reprocessing
Stickgold, R., Hobson, J. A., Fosse, R., & Fosse, M. (2001) · Science · doi:10.1126/science.1063530 · Cited by 762 · see citing works
Modes and models of forebrain cholinergic neuromodulation of cognition
Hasselmo, M. E., & Sarter, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.104 · Cited by 733 · see citing works
Theta and gamma oscillations predict encoding and retrieval of declarative memory
Osipova, D., Takashima, A., Oostenveld, R., Fernández, G., Maris, E., & Jensen, O. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1948-06.2006 · Cited by 671 · see citing works
The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas
Carhart-Harris, R. L., & Friston, K. J. (2010) · Brain · doi:10.1093/brain/awq010 · Cited by 574 · see citing works
Hasselmo, M. E. (2005) · Hippocampus · doi:10.1002/hipo.20116 · Cited by 502 · see citing works
Memory trace reactivation in hippocampal and neocortical neuronal ensembles
Sutherland, G. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00079-9 · Cited by 384 · see citing works
Astrocytes Mediate In Vivo Cholinergic-Induced Synaptic Plasticity
Navarrete, M., Perea, G., de Sevilla, D. F., Gómez-Gonzalo, M., Núñez, A., Martín, E. D., & Araque, A. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001259 · Cited by 387 · see citing works
Gu, N., Vervaeke, K., Hu, H., & Storm, J. F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086835 · Cited by 363 · see citing works
Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep
Poe, G. R., Nitz, D. A., McNaughton, B. L., & Barnes, C. A. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02310-0 · Cited by 318 · see citing works
Sleep-Dependent θ Oscillations in the Human Hippocampus and Neocortex
Cantero, J. L., Atienza, M., Stickgold, R., Kahana, M. J., Madsen, J. R., & Kocsis, B. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10897.2003 · Cited by 312 · see citing works
Howard, M. W., Fotedar, M. S., Datey, A. V., & Hasselmo, M. E. (2005) · Psychological Review · doi:10.1037/0033-295x.112.1.75 · Cited by 283 · see citing works
Larson, J., & Munkácsy, E. (2015) · Brain Research · doi:10.1016/j.brainres.2014.10.034 · Cited by 285 · see citing works
The role of REM sleep theta activity in emotional memory
Hutchison, I. C., & Rathore, S. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.01439 · Cited by 245 · see citing works
A neural network model of retrieval-induced forgetting
Norman, K. A., Newman, E. L., & Detre, G. (2007) · Psychological Review · doi:10.1037/0033-295x.114.4.887 · Cited by 218 · see citing works
Katona, L., Lapray, D., Viney, T. J., Oulhaj, A., Borhegyi, Z., Micklem, B. R., Klausberger, T., & Somogyi, P. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.007 · Cited by 169 · see citing works
McClean, P. L., Gault, V. A., Harriott, P., & Hölscher, C. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.12.023 · Cited by 193 · see citing works
Self-citationEphaptic coupling to endogenous electric field activity: Why bother?
Anastassiou, C. A., & Koch, C. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.09.002 · Cited by 171 · see citing works
Cholinergic control of GABA release: emerging parallels between neocortex and hippocampus
Lawrence, J. J. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.03.008 · Cited by 115 · see citing works
Hensch, T. K., Gordon, J. A., Brandon, E. P., McKnight, G. S., Idzerda, R. L., & Stryker, M. P. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02108.1998 · Cited by 117 · see citing works
Romcy‐Pereira, R., & Pavlides, C. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03808.x · Cited by 95 · see citing works
Hippocampal network oscillations at the interplay between innate anxiety and learned fear
Çalışkan, G., & Stork, O. (2019) · Psychopharmacology · doi:10.1007/s00213-018-5109-z · Cited by 72 · see citing works
Herman, P. A., Lundqvist, M., & Lansner, A. (2013) · Brain Research · doi:10.1016/j.brainres.2013.08.002 · Cited by 47 · see citing works
Karashima, A., Nakao, M., Honda, K., Iwasaki, N., Katayama, N., & Yamamoto, M. (2004) · Neuroscience Research · doi:10.1016/j.neures.2004.07.007 · Cited by 44 · see citing works
Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation
Almeida-Filho, D. G., Queiroz, C. M., & Ribeiro, S. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2886-9 · Cited by 38 · see citing works
Kloc, M. L., Chen, Y., Daglian, J. M., Holmes, G. L., Baram, T. Z., & Barry, J. M. (2023) · Hippocampus · doi:10.1002/hipo.23541 · Cited by 21 · see citing works
Karashima, A., Katayama, N., & Nakao, M. (2007) · Brain Research · doi:10.1016/j.brainres.2007.08.060 · Cited by 20 · see citing works
- Authors
- Hölscher, C., Anwyl, R., & Rowan, M. J.
- Affiliations
- Trinity College Dublin (IE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-08-15
- Volume
- 17
- Issue
- 16
- Pages
- 6470-6477
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6568346
- OpenAlex
- W1659775087
- Cited by
- 411
- References
- 2
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 7 · 2023: 17 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 4 · 2018: 17 · 2017: 13 · 2016: 10 · 2015: 15 · 2014: 20 · 2013: 17 · 2012: 14
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Health Research Board
- European Commission
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- long-term potentiation, depotentiation, hippocampal theta rhythm, theta phase, high-frequency stimulation, burst stimulation, CA1 stratum radiatum, synaptic plasticity, long-term depression, tail pinch, complex spikes, learning models, urethane anesthesia
- MeSH terms
- Animals, Hippocampus, Male, Membrane Potentials, Memory, Neuronal Plasticity, Theta Rhythm, Urethane, Rats, Wistar, Long-Term Potentiation, Anesthetics, Intravenous, Rats
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
