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.

In vivo endocannabinoid dynamics at the timescale of physiological and pathological neural activity / Farrell, Jordan S; Colangeli, Roberto; Dong, Ao; George, Antis G; Addo-Osafo, Kwaku; Kingsley, Philip J; Morena, Maria; Wolff, Marshal D; Dudok, Barna; He, Kaikai; Patrick, Toni A; Sharkey, Keith A; Patel, Sachin; Marnett, Lawrence J; Hill, Matthew N; Li, Yulong; Teskey, G Campbell; Soltesz, Ivan. - In: NEURON. - ISSN 0896-6273. - ELETTRONICO. - 109:15(2021), pp. 2398-2403.e4-2403.e4. [10.1016/j.neuron.2021.05.026]

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

Colangeli, Roberto
Secondo
;
2021-01-01

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.
2021
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/291530
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 30
  • ???jsp.display-item.citation.isi??? 25
social impact