The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
A hypothalamic circuit for the circadian control of aggression
Open accessAbstract
'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZ GABA) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZ GABA neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZ GABA transmission phase-dependently increases aggression. Finally, SPZ GABA-recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.
Overview
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
Verification
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?
In the citing paper
“A recent study in mice revealed that rhythms in the propensity of aggressive behaviours are modulated via a polysynaptic circuit from VIP neurons in the SCN to GABAergic neurons of the subparaventricular zone, which in turn innervate the ventromedial hypothalamus, an area known to regulate aggression283.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [283]
In the citing paper
“This chemogenetic study in mice reveals a neural circuit involving projections from the SCN to the ventromedial hypothalamus that drives time-of-day-dependent aggressive behaviours.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [283]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Coordination of circadian timing in mammals
Reppert, S. M., & Weaver, D. R. (2002) · Nature · doi:10.1038/nature00965 · Cited by 4,379
Rethinking the Emotional Brain
LeDoux, J. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.004 · Cited by 1,594
Welsh, D. K., Logothetis, D. E., Meister, M., & Reppert, S. M. (1995) · Neuron · doi:10.1016/0896-6273(95)90214-7 · Cited by 1,481
Motivation concepts in behavioral neuroscience
Berridge, K. C. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.02.004 · Cited by 1,302
Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons
Vong, L., Ye, C., Yang, Z., Choi, B. J., Chua, S. C., & Lowell, B. B. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.028 · Cited by 1,237
Self-citationVentromedial hypothalamic neurons control a defensive emotion state
Kunwar, P. S., Zelikowsky, M., Remedios, R., Cai, H., Balban, M. Y., Meister, M., & Anderson, D. J. (2015) · eLife · doi:10.7554/elife.06633 · Cited by 1,130
Neural mechanisms of aggression
Nelson, R. J., & Trainor, B. C. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2174 · Cited by 1,046
Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections
Petreanu, L., Huber, D., Sobczyk, A., & Svoboda, K. (2007) · Nature Neuroscience · doi:10.1038/nn1891 · Cited by 930
Functional identification of an aggression locus in the mouse hypothalamus
Lin, D., Boyle, M. P., Dollar, P., Lee, H., Lein, E. S., Perona, P., & Anderson, D. J. (2011) · Nature · doi:10.1038/nature09736 · Cited by 914
A Molecular Mechanism Regulating Rhythmic Output from the Suprachiasmatic Circadian Clock
Jin, X., Shearman, L. P., Weaver, D. R., Zylka, M. J., Vries, G. J. D., & Reppert, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)80959-9 · Cited by 891
Cited by
Sorted by citations
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
Neural mechanisms of aggression across species
Lischinsky, J. E., & Lin, D. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00715-2 · Cited by 276
Circadian rhythms in neurodegenerative disorders
Nassan, M. M., & Videnović, A. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00577-7 · Cited by 266
The physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168
A functional cellular framework for sex and estrous cycle-dependent gene expression and behavior
Knoedler, J. R., Inoue, S., Bayless, D. W., Yang, T., Tantry, A., Davis, C.-H. O., Leung, N. Y., Parthasarathy, S., Wang, G., Alvarado, M., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.031 · Cited by 168
Metadata
- Authors
- Todd, W. D., Fenselau, H., Wang, J. L., Zhang, R., Machado, N. L., Venner, A., Broadhurst, R. Y., Kaur, S., Lynagh, T., Olson, D. P., Lowell, B. B., Fuller, P. M., & Saper, C. B.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Boston Children's Hospital (US)
- Universidade Federal de Minas Gerais (BR)
- University of Copenhagen (DK)
- University of Michigan (US)
- Corresponding author
- Saper, Clifford B.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-04-09
- Volume
- 21
- Issue
- 5
- Pages
- 717-724
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5920747
- OpenAlex
- W2797554353
- Cited by
- 154
- References
- 58
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 16 · 2023: 19 · 2022: 18 · 2021: 21 · 2020: 22 · 2019: 14 · 2018: 18
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Alzheimer's Association (AARF-16-443613)
- California Institute of Technology
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (2014‐0)
- National Institutes of Health (HL00701-15, DK057521, DK089044, DK111401, HL095491, DK046200, NS073613, NS072337)
- National Institute on Aging (R03AG062883, P01AG009975)
- National Heart, Lung, and Blood Institute (P01HL095491, T32HL007901)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, R01DK075632, R01DK089044, P30DK046200, K08DK071561, R01DK111401, R01DK096010)
- National Institute of Neurological Disorders and Stroke (R01NS072337, R01NS092652, R01NS085477, R01NS103161, F32NS084582, R01NS073613)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- circadian clock, aggression, suprachiasmatic nucleus, GABAergic neurons, ventromedial hypothalamus, vasoactive intestinal peptide, attack behavior, sundowning, Alzheimer's disease, dementia, chemogenetic inhibition
- MeSH terms
- Aggression, Animals, Brain Mapping, Circadian Rhythm, Corticosterone, gamma-Aminobutyric Acid, Hypothalamus, Male, Mice, Inbred C57BL, Neural Pathways, Paraventricular Hypothalamic Nucleus, Suprachiasmatic Nucleus, Vasoactive Intestinal Peptide, Ventromedial Hypothalamic Nucleus, Excitatory Postsynaptic Potentials, Mice, Optogenetics
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
