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Hippocampal-dependent learning requires a functional circadian system
Open accessAbstract
Decades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an appropriate animal model. Surgical ablation of the suprachiasmatic nucleus (SCN) and clock gene knockouts eliminate rhythms, but also damage adjacent brain regions or cause developmental effects that may impair cognitive or other physiological functions. We developed a method that avoids these problems and eliminates rhythms by noninvasive means in Siberian hamsters (Phodopus sungorus). The present study evaluated cognitive function in arrhythmic animals by using a hippocampal-dependent learning task. Control hamsters exhibited normal circadian modulation of performance in a delayed novel-object recognition task. By contrast, arrhythmic animals could not discriminate a novel object from a familiar one only 20 or 60 min after training. Memory performance was not related to prior sleep history as sleep manipulations had no effect on performance. The GABA antagonist pentylenetetrazol restored learning without restoring circadian rhythms. We conclude that the circadian system is involved in memory function in a manner that is independent of sleep. Circadian influence on learning may be exerted via cyclic GABA output from the SCN to target sites involved in learning. Arrhythmic hamsters may have failed to perform this task because of chronic inhibitory signaling from the SCN that interfered with the plastic mechanisms that encode learning in the hippocampus.
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“In confirmation of these findings in mice, studies in Siberian hamsters also show that alterations in the photoperiod sometimes lead to loss of circadian rhyhtmicity and concomitant loss of recall of a novel object (Ruby et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Ruby et al., 2008
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Citations
Cites
Coordination of circadian timing in mammals
Reppert, S. M., & Weaver, D. R. (2002) · Nature · doi:10.1038/nature00965 · Cited by 4,379
Squire, L. R., Stark, C. E. L., & Clark, R. E. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144130 · Cited by 2,680
A functional analysis of circadian pacemakers in nocturnal rodents
Pittendrigh, C. S., & Daan, S. (1976) · Journal of Comparative Physiology A · doi:10.1007/bf01417856 · Cited by 2,129
Applications of the Morris water maze in the study of learning and memory
D’Hooge, R., & Deyn, P. P. D. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00067-4 · Cited by 2,083
Pittendrigh, C. S., & Daan, S. (1976) · Journal of Comparative Physiology ? A · doi:10.1007/bf01417860 · Cited by 1,636
Neural regulation of circadian rhythms.
Rusak, B., & Zucker, I. (1979) · Physiological Reviews · doi:10.1152/physrev.1979.59.3.449 · Cited by 1,402
Walker, M. P., & Stickgold, R. (2006) · Annual Review of Psychology · doi:10.1146/annurev.psych.56.091103.070307 · Cited by 1,075 · cited 2×
“literature that has described how sleep improves learning (29), there is evidence that short periods of sleep (e.”
BackgroundRecognition memory and the medial temporal lobe: a new perspective
Squire, L. R., Wixted, J. T., & Clark, R. E. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2154 · Cited by 1,059
Spatial memory, recognition memory, and the hippocampus
Broadbent, N. J., Squire, L. R., & Clark, R. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406344101 · Cited by 985
Watts, A. G., Swanson, L. W., & Sanchez‐Watts, G. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902580204 · Cited by 678
Dijk, D.-J., & Czeisler, C. A. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90841-9 · Cited by 628
Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance
Dijk, D., Duffy, J. F., & Czeisler, C. A. (1992) · Journal of Sleep Research · doi:10.1111/j.1365-2869.1992.tb00021.x · Cited by 602
GABA is the principal neurotransmitter of the circadian system
Moore, R. Y., & Speh, J. C. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90120-a · Cited by 555
Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome
Fernandez, F., Morishita, W., Zuniga, E., Nguyen, J., Blank, M., Malenka, R. C., & Garner, C. C. (2007) · Nature Neuroscience · doi:10.1038/nn1860 · Cited by 509
Stress response genes protect against lethal effects of sleep deprivation in Drosophila
Shaw, P. J., Tononi, G., Greenspan, R. J., & Robinson, D. F. (2002) · Nature · doi:10.1038/417287a · Cited by 488
Kleschevnikov, A. M., Belichenko, P. V., Villar, A. J., Epstein, C. J., Malenka, R. C., & Mobley, W. C. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1766-04.2004 · Cited by 459
Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation
Gais, S., & Born, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305404101 · Cited by 412
Constant light desynchronizes mammalian clock neurons
Ohta, H., Yamazaki, S., & McMahon, D. G. (2005) · Nature Neuroscience · doi:10.1038/nn1395 · Cited by 405
The Circadian Clock Mutation Alters Sleep Homeostasis in the Mouse
Naylor, E., Bergmann, B. M., Krauski, K., Zee, P. C., Takahashi, J. S., Vitaterna, M. H., & Turek, F. W. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-21-08138.2000 · Cited by 367
A functional analysis of circadian pacemakers in nocturnal rodents
Daan, S., & Pittendrigh, C. S. (1976) · Journal of Comparative Physiology A · doi:10.1007/bf01417858 · Cited by 301
Synaptic structural abnormalities in the Ts65Dn mouse model of down syndrome
Belichenko, P. V., Masliah, E., Kleschevnikov, A. M., Villar, A. J., Epstein, C. J., Salehi, A., & Mobley, W. C. (2004) · Journal of Comparative Neurology · doi:10.1002/cne.20337 · Cited by 297
A role for cryptochromesin sleep regulation
Wisor, J. P., O’Hara, B. F., Terao, A., Selby, C. P., Kilduff, T. S., Sancar, A., Edgar, D. M., & Franken, P. (2002) · BMC Neuroscience · doi:10.1186/1471-2202-3-20 · Cited by 289
Greenspan, R. J. (2001) · Nature Reviews Genetics · doi:10.1038/35072018 · Cited by 222
Circadian rhythms and reproduction
Boden, M. J., & Kennaway, D. J. (2006) · Reproduction · doi:10.1530/rep.1.00614 · Cited by 175
Suprachiasmatic nucleus lesion increases corticosterone secretion
Buijs, R. M., Kalsbeek, A., van der Woude, T. P., van Heerikhuize, J. J., & Shinn, S. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.6.r1186 · Cited by 149
Circadian temperature and wake rhythms of rats exposed to prolonged continuous illumination
Eastman, C. I., & Rechtschaffen, A. (1983) · Physiology & Behavior · doi:10.1016/0031-9384(83)90061-6 · Cited by 139
Light-induced suppression of the rat circadian system
Deprés-Brummer, P., Lévi, F., Metzger, G., & Touitou, Y. (1995) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1995.268.5.r1111 · Cited by 138
Multiphasic Retention Deficits at Periodic Intervals after Passive-Avoidance Learning
Holloway, F. A., & Wansley, R. A. (1973) · Science · doi:10.1126/science.180.4082.208 · Cited by 136
Morin, L. P., Goodless-Sanchez, N., Smale, L., & Moore, R. Y. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90240-2 · Cited by 133
Multiple retention deficits at periodic intervals after active and passive avoidance learning
Holloway, F. A., & Wansley, R. A. (1973) · Behavioral Biology · doi:10.1016/s0091-6773(73)80164-6 · Cited by 127
Ma, W., Cao, J., Tian, M., Cui, M., Han, H., Yang, Y., & Xu, L. (2007) · Neuroscience Research · doi:10.1016/j.neures.2007.06.1474 · Cited by 125
Discrimination of circadian phase in intact and suprachiasmatic nuclei-ablated rats
Mistlberger, R. E., de Groot, M. H. M., Bossert, J. M., & Marchant, E. G. (1996) · Brain Research · doi:10.1016/s0006-8993(96)00466-0 · Cited by 112
Suprachiasmatic and paraventricular control of photoperiodism in Siberian hamsters
Bittman, E. L., Bartness, T. J., Goldman, B. D., & DeVries, G. J. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.1.r90 · Cited by 109
Castel, M., & Morris, J. F. (2000) · Journal of Anatomy · doi:10.1046/j.1469-7580.2000.19610001.x · Cited by 100
Welberg, L., Thrivikraman, K. V., & Plotsky, P. M. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.11.011 · Cited by 98
Belenky, M. A., Yarom, Y., & Pickard, G. E. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21553 · Cited by 94
Perchance to dream: Solving the mystery of sleep through genetic analysis
Shaw, P. J., & Franken, P. (2002) · Journal of Neurobiology · doi:10.1002/neu.10167 · Cited by 91
Multiple retention deficit in passive avoidance in rats is eliminated by suprachiasmatic lesions
Stephan, F. K., & Kovacević, N. (1978) · Behavioral Biology · doi:10.1016/s0091-6773(78)92565-8 · Cited by 88
Age and time-of-day effects on learning and memory in a non-matching-to-sample test
Winocur, G., & Hasher, L. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.10.005 · Cited by 78
Circadian modulation of performance on an aversion-based place learning task in hamsters
Cain, S. W., Chou, T., & Ralph, M. R. (2003) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.07.001 · Cited by 65
Parent, M. B., Laurey, P. T., WILKNISS, S. M., & Gold, P. E. (1997) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1997.3769 · Cited by 59
MA, Y. J., Kelly, M. J., & RÖNNEKLEI, O. K. (1990) · Endocrinology · doi:10.1210/endo-127-6-2654 · Cited by 53
Degroot, A., & Parent, M. B. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02798-6 · Cited by 52
Mason, R. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90920-o · Cited by 52
Steinlechner, S., Stieglitz, A., & Ruf, T. (2002) · Journal of Biological Rhythms · doi:10.1177/074873040201700308 · Cited by 52
Homeostatic regulation of sleep in arrhythmic Siberian hamsters
Larkin, J. E., Yokogawa, T., Heller, H. C., Franken, P., & Ruby, N. F. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00676.2003 · Cited by 50
Sleep Onset Is Associated With Retrograde and Anterograde Amnesia
Wyatt, J. K., Bootzin, R. R., Anthony, J., & Bazant, S. (1994) · SLEEP · doi:10.1093/sleep/17.6.502 · Cited by 50
Ko, C. H., McDonald, R. J., & Ralph, M. R. (2003) · Biological Rhythm Research · doi:10.1076/brhm.34.2.177.14493 · Cited by 32
Prosser, R. A. (1998) · Journal of Biological Rhythms · doi:10.1177/074873098128999899 · Cited by 28
Hippocampal infusions of pyruvate reverse the memory-impairing effects of septal muscimol infusions
Krebs, D. L., & Parent, M. B. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.08.007 · Cited by 27
Ruby, N. F., Barakat, M. T., & Heller, H. C. (2004) · Journal of Biological Rhythms · doi:10.1177/0748730404268055 · Cited by 26
An Inbred Lineage of Djungarian Hamsters with a Strongly Attenuated Ability to Synchronize
Weinert, D., & Schöttner, K. (2007) · Chronobiology International · doi:10.1080/07420520701791588 · Cited by 20
Light induces c-fos and per1 expression in the suprachiasmatic nucleus of arrhythmic hamsters
Barakat, M. T., O’Hara, B. F., Cao, V. H., Heller, H. C., & Ruby, N. F. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00695.2004 · Cited by 14
Light suppresses frequency and endogenous amplitude of the circadian system in nocturnal animals
Witting, W., Boerma, D., Hoffen, G. C. K., Swaab, D. F., & Mirmiran, M. (1995) · Biological Rhythm Research · doi:10.1080/09291019509360351 · Cited by 13
Absence of a daily neuronal rhythm in the suprachiasmatic nuclei of acircadian Djungarian hamsters.
Margraf, R. R., Puchalski, W., & Lynch, G. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90367-g · Cited by 12
Book Review: Molecular Regulation of Circadian Rhythms in Drosophila and Mammals
Meyer-Bernstein, E. L., & Sehgal, A. (2001) · The Neuroscientist · doi:10.1177/107385840100700606 · Cited by 12
Cited by
Sorted by citations
Light as a central modulator of circadian rhythms, sleep and affect
LeGates, T. A., Fernandez, D. C., & Hattar, S. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3743 · Cited by 1,001
Light Affects Mood and Learning through Distinct Retina-Brain Pathways
Fernandez, D. C., Fogerson, P. M., Lazzerini Ospri, L., Thomsen, M. B., Layne, R. M., Severin, D., Zhan, J., Singer, J. H., Kirkwood, A., Zhao, H., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.004 · Cited by 505
Tranah, G. J., Blackwell, T., Stone, K. L., Ancoli‐Israel, S., Paudel, M. L., Ensrud, K. E., Cauley, J. A., Redline, S., Hillier, T. A., Cummings, S. R., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22468 · Cited by 525
Agorastos, A., Pervanidou, P., Chrousos, G. P., & Baker, D. G. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00118 · Cited by 385
“Memory processing, formation and consolidation are directly influenced by the circadian clock and stress (322, 324, 325).”
BackgroundCircadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance.
Liston, C., Cichon, J. M., Jeanneteau, F., Jia, Z., Chao, M. V., & Gan, W.-B. (2013) · Nature Neuroscience · doi:10.1038/nn.3387 · Cited by 358
Metadata
- Authors
- Ruby, N. F., Hwang, C. E., Wessells, C., Fernandez, F., Zhang, P., Sapolsky, R., & Heller, H. C.
- Affiliations
- Stanford University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-10-07
- Volume
- 105
- Issue
- 40
- Pages
- 15593-15598
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2563080
- OpenAlex
- W2140995643
- Cited by
- 234
- References
- 57
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 23 · 2020: 19 · 2019: 13 · 2018: 13 · 2017: 16 · 2016: 16 · 2015: 15 · 2014: 18 · 2013: 23 · 2012: 11
- FWCI
- 5.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (52003745)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- circadian rhythm, hippocampus-dependent learning, memory, Siberian hamster, cardiac arrhythmias, suprachiasmatic nucleus, GABAergic neurotransmission, pentylenetetrazole, novel object recognition
- MeSH terms
- Animals, Circadian Rhythm, Female, gamma-Aminobutyric Acid, Cricetinae, Hippocampus, Learning, Male, Pentylenetetrazole, Sleep, Phodopus
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