Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment
Open accessAbstract
Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we identify a novel, direct connection between the DA neurons of the ventral tegmental area (VTA) and the suprachiasmatic nucleus (SCN). We demonstrate that D1 dopamine receptor (Drd1) signaling within the SCN is necessary for properly timed resynchronization of activity rhythms to phase-shifted light:dark cycles and that elevation of DA tone through selective activation of VTA DA neurons accelerates photoentrainment. Our findings demonstrate a previously unappreciated role for direct DA input to the master circadian clock and highlight the importance of an evolutionarily significant relationship between the circadian system and the neuromodulatory circuits that govern motivational behaviors.
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?
SCN neuronal firing is reduced in these mice from young adulthood and progressively worsens with age, suggesting a weakened circadian pacemaker and a potential loss of dopaminergic modulation of circadian rhythms.
“SCN neuronal firing is also reduced in these mice from young adulthood and progressively worsens with age, suggesting a weakened circadian pacemaker276 and a potential loss of dopaminergic modulation of circadian rhythms via midbrain, striatal and SCN circuits277,278.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [277]
Re-entrainment of the SCN to phase shifts in the light-dark schedule is facilitated by dopaminergic projections from the ventral tegmental area to the SCN and is dependent on dopamine 1 receptor-expressing neurons in the SCN.
“This study shows re-entrainment of the SCN to phase shifts in the light–dark schedule is facilitated by dopaminergic projections from the ventral tegmental area to the SCN and is dependent on dopamine 1 receptor-expressing neurons in the SCN.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [277]
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
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907 · see citing works
Dopamine receptors: from structure to function
MISSALE, C., NASH, S. R., ROBINSON, S. W., JABER, M., & CARON, M. G. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.1.189 · Cited by 3,633 · see citing works
Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat
Moore, R. Y., & Eichler, V. B. (1972) · Brain Research · doi:10.1016/0006-8993(72)90054-6 · Cited by 2,135 · see citing works
Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., & Roth, B. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700293104 · Cited by 2,046 · see citing works
Stephan, F. K., & Zucker, I. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.6.1583 · Cited by 2,039 · see citing works
Entrainment of the circadian clock in the liver by feeding
Stokkan, K.-A., Yamazaki, S., Tei, H., Sakaki, Y., & Menaker, M. (2001) · Science · doi:10.1126/science.291.5503.490 · Cited by 1,800 · see citing works
Welsh, D. K., Logothetis, D., Meister, M., & Reppert, S. (1995) · Neuron · doi:10.1016/0896-6273(95)90214-7 · Cited by 1,535 · see citing works
Suprachiasmatic Nucleus: Cell Autonomy and Network Properties
Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135919 · Cited by 1,216 · see citing works
Physiology of Circadian Entrainment
Golombek, D. A., & Rosenstein, R. E. (2010) · Physiological Reviews · doi:10.1152/physrev.00009.2009 · Cited by 1,103 · see citing works
Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease
Wulff, K., Gatti, S., Wettstein, J. G., & Foster, R. G. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2868 · Cited by 1,055 · see citing works
Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision
Güler, A. D., Ecker, J. L., Lall, G. S., Haq, S., Altimus, C. M., Liao, H., Barnard, A. R., Cahill, H. B., Badea, T. C., Zhao, H., et al. (2008) · Nature · doi:10.1038/nature06829 · Cited by 872 · see citing works
Self-citationVTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors
Eban-Rothschild, A., Rothschild, G., Giardino, W. J., Jones, J. R., & de Lecea, L. (2016) · Nature Neuroscience · doi:10.1038/nn.4377 · Cited by 583 · see citing works
Takahashi, J. S., DeCoursey, P. J., Bauman, L., & Menaker, M. (1984) · Nature · doi:10.1038/308186a0 · Cited by 528 · see citing works
Photoreceptive net in the mammalian retina
Provencio, I., Rollag, M. D., & Castrucci, A. M. D. L. (2002) · Nature · doi:10.1038/415493a · Cited by 472 · see citing works
Orchestrating time: arrangements of the brain circadian clock
Antle, M. C., & Silver, R. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.01.003 · Cited by 463 · see citing works
Chronic jet-lag increases mortality in aged mice
Davidson, A. J., Sellix, M. T., Daniel, J., Yamazaki, S., Menaker, M., & Block, G. D. (2006) · Current Biology · doi:10.1016/j.cub.2006.09.058 · Cited by 427 · see citing works
Clock controls circadian period in isolated suprachiasmatic nucleus neurons
Herzog, E. D., Takahashi, J. S., & Block, G. D. (1998) · Nature Neuroscience · doi:10.1038/3708 · Cited by 387 · see citing works
Dissecting the diversity of midbrain dopamine neurons
Roeper, J. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.03.003 · Cited by 372 · see citing works
Food availability and daily biological rhythms.
Boulos, Z., & Terman, M. (1980) · Neuroscience and Biobehavioral Reviews · doi:10.1016/0149-7634(80)90010-x · Cited by 367 · see citing works
Neurobiology of food anticipatory circadian rhythms
Mistlberger, R. E. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.015 · Cited by 345 · see citing works
Diversity of Transgenic Mouse Models for Selective Targeting of Midbrain Dopamine Neurons
Lammel, S., Steinberg, E. E., Földy, C., Wall, N. R., Beier, K. T., Luo, L., & Malenka, R. C. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.036 · Cited by 345 · see citing works
Remote Control of Neuronal Signaling
Rogan, S. C., & Roth, B. L. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003020 · Cited by 339 · see citing works
Targeted gene expression in dopamine and serotonin neurons of the mouse brain
Zhuang, X., Masson, J., Gingrich, J. A., Rayport, S., & Hen, R. (2004) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2004.09.020 · Cited by 316 · see citing works
Anticipation of 24-hr feeding schedules in rats with lesions of the suprachiasmatic nucleus
Stephan, F. K., Swann, J. M., & Sisk, C. L. (1979) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(79)90415-1 · Cited by 310 · see citing works
Van Veen, M. M., Kooij, J. J. S., Boonstra, A. M., Gordijn, M. C. M., & Van Someren, E. J. W. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.12.032 · Cited by 300 · see citing works
Krieger, D. T., Hauser, H., & Krey, L. C. (1977) · Science · doi:10.1126/science.877566 · Cited by 297 · see citing works
Retinal Dopamine Mediates Multiple Dimensions of Light-Adapted Vision
Jackson, C. R., Ruan, G.-X., Aseem, F., Abey, J., Gamble, K. L., Stanwood, G. D., Palmiter, R. D., Iuvone, P. M., & McMahon, D. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0711-12.2012 · Cited by 277 · see citing works
Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities
Altimus, C. M., Güler, A. D., Alam, N. M., Arman, A. C., Prusky, G. T., Sampath, A. P., & Hattar, S. S. (2010) · Nature Neuroscience · doi:10.1038/nn.2617 · Cited by 252 · see citing works
Self-citationNirenberg, M. J., Chan, J., Liu, Y., Edwards, R. H., & Pickel, V. M. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-13-04135.1996 · Cited by 240 · see citing works
A clinical approach to circadian rhythm sleep disorders
Barion, A., & Zee, P. C. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2006.11.017 · Cited by 214 · see citing works
Kizer, J. S., Palkovits, M., & Brownstein, M. (1976) · Brain Research · doi:10.1016/0006-8993(76)90192-x · Cited by 198 · see citing works
Circadian disruption and metabolic disease: Findings from animal models
Arble, D. M., Ramsey, K. M., Bass, J., & Turek, F. W. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.08.003 · Cited by 192 · see citing works
Cahill, G., & Besharse, J. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-10-02959.1991 · Cited by 190 · see citing works
A highly tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal
Blum, I. D., Zhu, L., Moquin, L., Kokoeva, M. V., Gratton, A., Giros, B., & Storch, K.-F. (2014) · eLife · doi:10.7554/elife.05105 · Cited by 168 · see citing works
An Autonomous Circadian Clock in the Inner Mouse Retina Regulated by Dopamine and GABA
Ruan, G.-X., Allen, G. C., Yamazaki, S., & McMahon, D. G. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060249 · Cited by 164 · see citing works
Cao, R., Robinson, B., Xu, H., Gkogkas, C. G., Khoutorsky, A., Alain, T., Yanagiya, A., Nevarko, T., Liu, A. C., Amir, S., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.026 · Cited by 143 · see citing works
Circadian rhythmicity in dopamine content of mammalian retina: role of the photoreceptors
Doyle, S. E., McIvor, W. E., & Menaker, M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01149.x · Cited by 133 · see citing works
Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior
Jones, J. R., Tackenberg, M. C., & McMahon, D. G. (2015) · Nature Neuroscience · doi:10.1038/nn.3937 · Cited by 133 · see citing works
Circadian insights into dopamine mechanisms
Mendoza, J., & Challet, É. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.07.081 · Cited by 124 · see citing works
Viswanathan, N., Weaver, D. R., Reppert, S. M., & Davis, F. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05393.1994 · Cited by 102 · see citing works
Gallardo, C. M., Darvas, M., Oviatt, M., Chang, C. H., Michalik, M. J., Huddy, T. F., Meyer, E. E., Shuster, S. A., Aguayo, A., Hill, E. M., et al. (2014) · eLife · doi:10.7554/elife.03781 · Cited by 98 · see citing works
D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei.
Weaver, D. R., Rivkees, S. A., & Reppert, S. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9201 · Cited by 90 · see citing works
Circadian timing in health and disease
Maywood, E. S., O'Neill, J. S., Wong, G. K. Y., Reddy, A. B., & Hastings, M. H. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53015-8 · Cited by 89 · see citing works
Yamanaka, Y., Honma, S., & Honma, K.-I. (2008) · Genes to Cells · doi:10.1111/j.1365-2443.2008.01183.x · Cited by 82 · see citing works
Bobrzynska, K. J., & Mrosovsky, N. (1998) · Journal of Comparative Physiology A · doi:10.1007/s003590050175 · Cited by 81 · see citing works
Non‐photic signalling in the suprachiasmatic nucleus
Hastings, M. H., Duffield, G. E., Ebling, F. J. P., Kidd, A., Maywood, E. S., & Schurov, I. (1997) · Biology of the Cell · doi:10.1016/s0248-4900(98)80005-1 · Cited by 69 · see citing works
Smyllie, N. J., Chesham, J. E., Hamnett, R., Maywood, E. S., & Hastings, M. H. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511351113 · Cited by 67 · see citing works
Abnormalities in sleep patterns in individuals at risk for psychosis and bipolar disorder
Zanini, M. A., Castro, J., Cunha, G. R., Asevedo, E., Pan, P. M., Bittencourt, L., Coelho, F. M., Tufik, S., Gadelha, A., Bressan, R. A., et al. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.08.023 · Cited by 64 · see citing works
Jurkevich, A., Barth, S. W., Kuenzel, W. J., K�HLER, A., & Großmann, R. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990524)408:1 · Cited by 59 · see citing works
TONIC AND PHASIC EFFECTS OF LIGHT IN THE ENTRAINMENT OF CIRCADIAN RHYTHMS
Daan, S. (1977) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1977.tb39716.x · Cited by 57 · see citing works
Gore, B. B., & Zweifel, L. S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5532-12.2013 · Cited by 50 · see citing works
Self-citationNakamura, T., Sato, A., Kitsukawa, T., Momiyama, T., Yamamori, T., & Sasaoka, T. (2014) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2014.00056 · Cited by 48 · see citing works
Deletion of GAD67 in dopamine receptor‐1 expressing cells causes specific motor deficits
Heusner, C. L., Beutler, L. R., Houser, C. R., & Palmiter, R. D. (2008) · genesis · doi:10.1002/dvg.20405 · Cited by 46 · see citing works
Ugrumov, M. V., Tixier‐Vidal, A., Taxi, J., Thibault, J., & Mitskevich, M. S. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90339-4 · Cited by 44 · see citing works
Sleep in schizophrenia: time for closer attention
Wilson, S., & Argyropoulos, S. (2012) · British Journal of Psychiatry · doi:10.1192/bjp.bp.111.104091 · Cited by 39 · see citing works
Enhanced reward-related responding following cholera toxin infusion into the nucleus accumbens
Kelley, A. E., & Holahan, M. R. (1997) · Synapse · doi:10.1002/(sici)1098-2396(199705)26:1 · Cited by 31 · see citing works
Duffield, Hastings, M. H., & Ebling, E. (1998) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1998.00274.x · Cited by 28 · see citing works
Strother, W. N., Norman, A. B., & Lehman, M. N. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(97)00205-8 · Cited by 27 · see citing works
Bender, M., Drago, J., & Rivkees, S. A. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(97)00161-7 · Cited by 25 · see citing works
Lin, L., & Pivorun, E. B. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90505-4 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Generation of circadian rhythms in the suprachiasmatic nucleus
Hastings, M. H., Maywood, E. S., & Brancaccio, M. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0026-z · Cited by 1,065 · see citing works
Rhythms of life: circadian disruption and brain disorders across the lifespan
Logan, R. W., & McClung, C. A. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0088-y · Cited by 713 · see citing works
Vadnie, C. A., & McClung, C. A. (2017) · Neural Plasticity · doi:10.1155/2017/1504507 · Cited by 199 · see citing works
The brain’s reward system in health and disease
Lewis, R. G., Florio, E., Punzo, D., & Borrelli, E. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-81147-1_4 · Cited by 170 · see citing works
Dorsal tegmental dopamine neurons gate associative learning of fear
Groessl, F., Munsch, T., Meis, S., Griessner, J., Kaczanowska, J., Pliota, P., Kargl, D., Badurek, S., Kraitsy, K., Rassoulpour, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0174-5 · Cited by 118 · see citing works
Disrupted sleep and circadian rhythms in schizophrenia and their interaction with dopamine signaling
Ashton, A., & Jagannath, A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00636 · Cited by 106 · see citing works
- Authors
- Grippo, R. M., Purohit, A. M., Zhang, Q., Zweifel, L. S., & Güler, A. D.
- Affiliations
- University of Virginia (US)
- University of Washington (US)
- Corresponding author
- Güler, Ali D.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 27
- Issue
- 16
- Pages
- 2465-2475.e3
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC5568465
- OpenAlex
- W2743429878
- Cited by
- 140
- References
- 60
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 15 · 2023: 23 · 2022: 17 · 2021: 13 · 2020: 11 · 2019: 14 · 2018: 15 · 2017: 2
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH National Institute of Mental Health (NIMH) (R01MH104450)
- NIH National Institute of General Medicinal Sciences (NIGMS) (R01GM11937)
- University of Virginia
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- dopamine, suprachiasmatic nucleus, ventral tegmental area, circadian entrainment, light entrainment, dopamine D1 receptor, circadian clock, phase shifting, light-dark cycle, neuromodulation, circadian rhythm
- MeSH terms
- Animals, Dopamine, Male, Mesencephalon, Mice, Inbred C57BL, Suprachiasmatic Nucleus, Ventral Tegmental Area, Mice, Circadian Clocks, Dopaminergic Neurons
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
