Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain.
Yue Hu, Wenjie Du, Jiangtao Qi, Huoqing Luo, Zhao Zhang, Mengqiang Luo, Yingwei Wang
Elife March 21, 2024 DOI: 10.7554/eLife.88420 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Comparative animal study Peer reviewed |
|---|---|
| Population | Mouse brain |
| Interventions | Ketamine Isoflurane |
| Topics | Ketamine Esketamine |
| Keywords | C-fos Functional network Isoflurane Anesthesia anaesthesia Anesthetic Anaesthetic Neuroscience neurobiology Brain research Neural science Consciousness unconsciousness Awareness Drug mechanisms Animal studies mouse |
| Citations | 27 |
| Key points | Ketamine activates higher-order cortical networks in a top-down manner while isoflurane primarily affects hypothalamic and autonomic regions in a bottom-up manner, yet both anesthetics share effects on sensory, cognitive, and reward pathways. |
Abstract
Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the mouse brain, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings reveal that KET activates a wide range of brain regions, notably in the cortical and subcortical nuclei involved in sensory, motor, emotional, and reward processing, with the temporal association areas (TEa) as a strong hub, suggesting a top-down mechanism affecting consciousness by primarily targeting higher order cortical networks. In contrast, ISO predominantly influences brain regions in the hypothalamus, impacting neuroendocrine control, autonomic function, and homeostasis, with the locus coeruleus (LC) as a connector hub, indicating a bottom-up mechanism in anesthetic-induced unconsciousness. KET and ISO both activate brain areas involved in sensory processing, memory and cognition, reward and motivation, as well as autonomic and homeostatic control, highlighting their shared effects on various neural pathways. In conclusion, our results highlight the distinct but overlapping effects of KET and ISO, enriching our understanding of the mechanisms underlying general anesthesia.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 3
- Cannabidiol Mitigates Ketamine-Induced Hyperlocomotion Via Allosteric Potentiation of Ventral Tegmental Glycine Receptor α1 Signaling. Biological Psychiatry March 16, 2026
- Cellular and Microcircuit Mechanisms of Anesthetic Disruption of Conscious-State Organization. Cells August 18, 2026
- Repeated ketamine exposure induces psychotic-like behaviors in mice via DRD1-mediated phosphorylation of p-Thr34 DARPP-32 and p-Ser10 histone H3 Cell Biology and Toxicology November 25, 2025
Cites 3
- Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Anesthesiology May 22, 2013
- Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness Frontiers in Neural Circuits June 20, 2017
- Experimental and theoretical approaches to conscious processing. Neuron April 28, 2011