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

Jordan S. Farrell*, Roberto Colangeli, Ao Dong, Antis G. George, Kwaku Addo-Osafo, Philip J. Kingsley, Maria Morena, Marshal D. Wolff, Barna Dudok, Kaikai He, Toni A. Patrick, Keith A. Sharkey, Sachin Patel, Lawrence J. Marnett, Matthew N. Hill, Yulong Li, G. Campbell Teskey, Ivan Soltesz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2398-2403.e4
JournalNeuron
Volume109
Issue number15
DOIs
StatePublished - Aug 4 2021
Externally publishedYes

Keywords

  • 2-AG
  • AEA
  • COX-2
  • EP
  • MAGL
  • PGE
  • endocannabinoid
  • postictal hypoxia
  • prostaglandin
  • seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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