2. Academic Validation
  3. In vivo endocannabinoid dynamics at the timescale of physiological and pathological neural activity

In vivo endocannabinoid dynamics at the timescale of physiological and pathological neural activity

  • Neuron. 2021 Aug 4;109(15):2398-2403.e4. doi: 10.1016/j.neuron.2021.05.026.
Jordan S Farrell 1,  Roberto Colangeli 2,  Ao Dong 3,  Antis G George 2,  Kwaku Addo-Osafo 2,  Philip J Kingsley 4,  Maria Morena 2,  Marshal D Wolff 2,  Barna Dudok 5,  Kaikai He 3,  Toni A Patrick 6,  Keith A Sharkey 7,  Sachin Patel 6,  Lawrence J Marnett 4,  Matthew N Hill 2,  Yulong Li 3,  G Campbell Teskey 2,  Ivan Soltesz 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Anatomy and Cell Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: [email protected].
  • 2 Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Anatomy and Cell Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
  • 3 State Key Laboratory of Membrane Biology, School of Life Sciences, PKU-THU Center for Life Sciences, IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
  • 4 A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
  • 5 Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
  • 6 Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 7 Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
PMID: 34352214 DOI: 10.1016/j.neuron.2021.05.026
Abstract

The brain's endocannabinoid system is a powerful controller of neurotransmitter release, shaping synaptic communication under physiological and pathological conditions. However, our understanding of endocannabinoid signaling in vivo is limited by the inability to measure their changes at timescales commensurate with the high lability of lipid signals, leaving fundamental questions of whether, how, and which endocannabinoids fluctuate with neural activity unresolved. Using novel imaging approaches in awake behaving mice, we now demonstrate that the endocannabinoid 2-arachidonoylglycerol, not anandamide, is dynamically coupled to hippocampal neural activity with high spatiotemporal specificity. Furthermore, we show that seizures amplify the physiological endocannabinoid increase by orders of magnitude and drive the downstream synthesis of vasoactive prostaglandins that culminate in a prolonged stroke-like event. These results shed new LIGHT on normal and pathological endocannabinoid signaling in vivo.

Keywords

2-AG; AEA; COX-2; EP(1); MAGL; PGE(2); endocannabinoid; postictal hypoxia; prostaglandin; seizure.

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