ArticleProceedings of the National Academy of Sciences of the United States of America2015
Distinct roles for GABA across multiple timescales in mammalian circadian timekeeping.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 3 of them syntheses that pooled it.
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Who cites it
92 citing papers in PubMed, 3 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Systematic review of drugs that modify the circadian system's phase-shifting responses to light exposure.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Pooled it
- Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review.Frontiers in neuroscience · 2020Pooled it
- Meta-analysis of transcriptomic datasets identifies genes enriched in the mammalian circadian pacemaker.Nucleic acids research · 2017Pooled it
- Attractive and repulsive couplings between circadian pacemaker neurons promote entrainment to light-dark cycles with after-effect.Npj biological timing and sleep · 2026Article
- Article
- A compartmentalized SCN model explains temperature resistance through interregional phase differences.PLoS computational biology · 2026Article
- Reconsidering mammalian circadian organization.Neurobiology of sleep and circadian rhythms · 2026Article
- A GABAergic neural circuit from the suprachiasmatic nucleus to DG drives cognitive impairment in migraine mice.The journal of headache and pain · 2026Article
- Article
- An Automated Organotypic SCN Culture System Revealing Novel Insights into VIP Regulation of Circadian Rhythm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exercise and neural circuit stability in early Alzheimer's disease: evidence across memory, executive, cholinergic, and circadian systems.Frontiers in aging neuroscience · 2026Review
- Ocean acidification induces changes in circadian alternative splicing profiles in a coral reef fish.Scientific reports · 2025Article
- Seasonal timing and interindividual differences in shiftwork adaptation.NPJ digital medicine · 2025Article
- GABA regulates metabolic reprogramming to mediate the development of brain metastasis in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- GABAergic signalling in the suprachiasmatic nucleus is required for coherent circadian rhythmicity.The European journal of neuroscience · 2024Article
- Enhancing Bioluminescence Imaging of Cultured Tissue Explants Using Optical Telecompression.Sensors (Basel, Switzerland) · 2024Article
- Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity.Environmental science and ecotechnology · 2024Article
- GABAProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward.Journal of biological rhythms · 2024Review
- Neuronal reprogramming of mouse and human fibroblasts using transcription factors involved in suprachiasmatic nucleus development.iScience · 2024Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The suprachiasmatic nuclei (SCN), the central circadian pacemakers in mammals, comprise a multiscale neuronal system that times daily events. We use recent advances in graphics processing unit computing to generate a multiscale model for the SCN that resolves cellular electrical activity down to the timescale of individual action potentials and the intracellular molecular events that generate circadian rhythms. We use the model to study the role of the neurotransmitter GABA in synchronizing circadian rhythms among individual SCN neurons, a topic of much debate in the circadian community. The model predicts that GABA signaling has two components: phasic (fast) and tonic (slow). Phasic GABA postsynaptic currents are released after action potentials, and can both increase or decrease firing rate, depending on their timing in the interspike interval, a modeling hypothesis we experimentally validate; this allows flexibility in the timing of circadian output signals. Phasic GABA, however, does not significantly affect molecular timekeeping. The tonic GABA signal is released when cells become very excited and depolarized; it changes the excitability of neurons in the network, can shift molecular rhythms, and affects SCN synchrony. We measure which neurons are excited or inhibited by GABA across the day and find GABA-excited neurons are synchronized by-and GABA-inhibited neurons repelled from-this tonic GABA signal, which modulates the synchrony in the SCN provided by other signaling molecules. Our mathematical model also provides an important tool for circadian research, and a model computational system for the many multiscale projects currently studying brain function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.