The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
A neural circuit for circadian regulation of arousal
Abstract
An unknown aspect of behavioral state regulation is how the circadian oscillator of the suprachiasmatic nucleus (SCN) regulates sleep and waking. In this report, we describe the necessary elements for a circuit that provides circadian regulation of arousal. Trans-synaptic retrograde tracing revealed a prominent indirect projection from the SCN to the noradrenergic nucleus locus coeruleus (LC), a brain arousal system. Double-labeling experiments revealed several possible links between the SCN and the LC, including the dorsomedial (DMH) and paraventricular hypothalamic nuclei (PVN), as well as medial and ventrolateral pre-optic areas. Lesion studies confirmed that the DMH is a substantial relay in this circuit. Next, neurophysiology experiments revealed circadian variations in LC impulse activity. Lesions of the DMH eliminated these circadian changes in LC activity, confirming the functionality of the SCN-DMH-LC circuit. These results reveal mechanisms for regulation of circadian and sleep-waking functions.
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
“Sympathovagal balance is lowest during REM sleep, when the locus coeruleus, the main brain source of catecholamine biosynthesis, is silent.71”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [71]
In the citing paper
“and are important for transitions from focused attention to behavioral flexibility (Aston-Jones et al., 2001)”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Aston-Jones et al., 2001
In the citing paper
“For example, projections from the SCN to the locus coeruleus (LC) facilitate circadian regulation of noradrenergic activity”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Aston-Jones et al., 2001
In the citing paper
“The neuroanatomical circuit mediating circadian regulation of arousal is a multisynaptic pathway between the SCN and the noradrenergic neurons of the LC (Aston-Jones et al., 2001; Deurveilher and Semba, 2005).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Aston-Jones et al., 2001
In the citing paper
“The functional importance of this circuit was demonstrated by the findings that lesions of the DMH eliminate the circadian rhythm in LC neuronal activity, whereas lesions of the LC decrease the amplitude of circadian rhythms of slow-wave activity in the cortex (Aston-Jones et al., 2001).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Aston-Jones et al., 2001
In the citing paper
“As shown by neuroanatomical tract-tracing as well as lesion studies, the neurons in the SCN, which receives retinal input, project to the dorsomedial hypothalamus (DMH), which in turn projects to the LC (Aston-Jones et al., 2001; Deurveilher and Semba, 2005).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Aston-Jones et al., 2001
In the citing paper
“For example, an indirect projection from the SCN to the locus coeruleus appears to regulate the circadian rhythm in noradrenergic neuronal activity (Aston-Jones et al., 2001).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Aston-Jones et al., 2001
In the citing paper
“Indeed some of the major neurotransmitters that have been implicated in mood regulation, including serotonin, norepinephrine and dopamine, have a circadian rhythm in their levels, release, and synthesis-related enzymes (Weiner et al., 1992; Shieh et al., 1997; Aston-Jones et al., 2001; Barassin et al., 2002; Khaldy et al., 2002; Castaneda et al., 2004; Weber et al., 2004; Malek et al., 2005).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Aston-Jones et al., 2001
Citations
Cites
Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501
Paxinos, G. (1985) · Cited by 3,715
Neurons containing hypocretin (orexin) project to multiple neuronal systems
Peyron, C., Tighe, D. K., van den Pol, A. N., de Lecea, L., Heller, H. C., Sutcliffe, J. G., & Kilduff, T. S. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09996.1998 · Cited by 3,466
Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095
Psychopharmacology: The Fourth Generation of Progress
Bloom, F. E., & Kupfer, D. J. (1995) · Medical Entomology and Zoology · Cited by 2,985
Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P. J., Nishino, S., & Mignot, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81965-0 · Cited by 2,613
Aston-Jones, G., & Bloom, F. (1981) · The Journal of Neuroscience · doi:10.1523/jneurosci.01-08-00876.1981 · Cited by 1,960
Self-citationNucleus locus ceruleus: new evidence of anatomical and physiological specificity
Foote, S. L., Bloom, F. E., & Aston-Jones, G. (1983) · Physiological Reviews · doi:10.1152/physrev.1983.63.3.844 · Cited by 1,901
Self-citationBrain Maps: Structure of the Rat Brain
Swanson, L. W. (1992) · Medical Entomology and Zoology · Cited by 1,878
Suprachiasmatic nucleus : the mind's clock
Klein, D. C., Moore, R. Y., & Reppert, S. M. (1991) · Cited by 1,715
Flagged first, then by citations
Cited by
Sorted by citations
Hypothalamic regulation of sleep and circadian rhythms
Saper, C. B., Scammell, T. E., & Lu, J. (2005) · Nature · doi:10.1038/nature04284 · Cited by 2,804
The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease
Hampel, H., Mesulam, M.-M., Cuello, A. C., Farlow, M. R., Giacobini, E., Grossberg, G. T., Khachaturian, A. S., Vergallo, A., Cavedo, E., Snyder, P. J., et al. (2018) · Brain · doi:10.1093/brain/awy132 · Cited by 1,918
Control 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
Mammalian circadian biology: elucidating genome-wide levels of temporal organization
Lowrey, P. L., & Takahashi, J. S. (2004) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.5.061903.175925 · Cited by 976
The Neurobiology of Sleep: Genetics, cellular physiology and subcortical networks
Pace-Schott, E. F., & Hobson, J. A. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn895 · Cited by 937
Metadata
- Authors
- Aston-Jones, G., Chen, S., Zhu, Y., & Oshinsky, M. L.
- Affiliations
- Long Island Jewish Medical Center (US)
- University of Pennsylvania (US)
- Thomas Jefferson University (US)
- Venue
- Nature Neuroscience
- Published
- 2001-07
- Volume
- 4
- Issue
- 7
- Pages
- 732-738
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1488974332
- Cited by
- 632
- References
- 51
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 19 · 2023: 23 · 2022: 14 · 2021: 20 · 2020: 23 · 2019: 16 · 2018: 38 · 2017: 21 · 2016: 31 · 2015: 23 · 2014: 23 · 2013: 22 · 2012: 35
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS024698, NS 24698)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- circadian rhythm, arousal, suprachiasmatic nucleus, locus coeruleus, noradrenergic system, dorsomedial hypothalamus, paraventricular nucleus, preoptic area, sleep-wake regulation, circadian oscillations, neural circuits, retrograde tracing
- MeSH terms
- Animals, Arousal, Circadian Rhythm, Electrophysiology, Hypothalamus, Immunohistochemistry, Locus Coeruleus, Male, Microinjections, Microscopy, Fluorescence, Herpesvirus 1, Suid, Suprachiasmatic Nucleus, Rats, Sprague-Dawley, 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
