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.
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DOI：
10.1016/j.neuron.2021.05.026
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发表时间：
2021-08-04
期刊：
影响因子：
16.2
通讯作者：
Soltesz I
中科院分区：
文献类型：
--
作者：
Farrell JS;Colangeli R;Dong A;George AG;Addo-Osafo K;Kingsley PJ;Morena M;Wolff MD;Dudok B;He K;Patrick TA;Sharkey KA;Patel S;Marnett LJ;Hill MN;Li Y;Teskey GC;Soltesz I
大脑的内源性大麻素系统是神经递质释放的强大控制器，在生理和病理条件下塑造突触通信。然而，我们对内源性大麻素信号在体内的理解是有限的，因为无法测量它们在与脂质信号的高不稳定性相称的时间尺度上的变化，留下了一些基本问题，即内源性大麻素是否、如何以及哪些内源性大麻素随着神经活动而波动。使用新的成像方法在清醒的行为小鼠，我们现在证明，内源性大麻素2-花生四烯酸甘油，而不是anandamide，是动态耦合到海马神经活动与高时空特异性。此外，我们发现，癫痫发作放大了生理性内源性大麻素的数量级增加，并驱动下游合成的血管活性肾上腺素，最终在一个长期的中风样事件。这些结果为体内正常和病理性内源性大麻素信号传导提供了新的线索。Farrell等人使用遗传编码的传感器解决了海马内源性大麻素信号传导的分子身份和时空动力学。与生理活动相比，癫痫发作导致过量的2-AG水平，为延长的卒中样事件提供底物。
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 if, 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. Farrell et al. resolve the molecular identity and spatiotemporal dynamics of hippocampal endocannabinoid signaling in vivo using a genetically encoded sensor. Compared to physiological activity, seizures result in excessive 2-AG levels, providing substrate for a prolonged stroke-like event.
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影响因子：
34.7
作者：
Soltesz, Ivan;Alger, Bradley E.;Kano, Masanobu;Lee, Sang-Hun;Lovinger, David M.;Ohno-Shosaku, Takako;Watanabe, Masahiko
通讯作者：
Watanabe, Masahiko
影响因子：
25
作者：
Di Marzo, Vincenzo
通讯作者：
Di Marzo, Vincenzo
影响因子：
64.8
作者：
Stella, N;Schweitzer, P;Piomelli, D
通讯作者：
Piomelli, D
影响因子：
14.5
作者：
Gaxiola-Valdez, Ismael;Singh, Shaily;Federico, Paolo
通讯作者：
Federico, Paolo
影响因子：
4.6
作者：
Farrell, Jordan S.;Colangeli, Roberto;Teskey, G. Campbell
通讯作者：
Teskey, G. Campbell