Inhibitory neurotransmission drives endocannabinoid degradation to promote memory consolidation.
Inhibitory neurotransmission drives endocannabinoid degradation to promote memory consolidation.
复制标题
抑制性神经传递驱动内源性大麻素降解以促进记忆巩固。
DOI：
10.1038/s41467-020-20121-3
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发表时间：
2020-12-17
影响因子：
16.6
通讯作者：
Liu SJ
中科院分区：
文献类型：
--
作者：
Dubois CJ;Fawcett-Patel J;Katzman PA;Liu SJ
内源性大麻素逆行调节突触传递，其丰度受内源性大麻素合成和降解之间的微妙平衡控制。虽然常见的假设是“按需”释放决定了内源性大麻素信号，但它们的快速降解预计将控制内源性大麻素作用的时间分布，并可能影响神经元信号转导。在这里，我们表明，通过恐惧条件反射形成的记忆选择性地加速了小脑中内源性大麻素的降解。学习诱导了GABA释放的持续增加，这是推动内源性大麻素降解变化的原因。相反，小脑浦肯野细胞的GQ-DREADD激活增强了内源性大麻素信号，并损害了记忆巩固。我们的发现发现了GABA和内源性大麻素系统之间以前未被认识到的相互作用，其中GABA信号加速内源性大麻素的降解，并触发一种形式的学习诱导的变塑性。内源性大麻素的水平受其合成和降解之间的微妙平衡控制。在这里，作者表明，通过恐惧条件反射形成的记忆通过持续增加GABA的释放，选择性地加速小脑中内源性大麻素的降解。
Endocannabinoids retrogradely regulate synaptic transmission and their abundance is controlled by the fine balance between endocannabinoid synthesis and degradation. While the common assumption is that “on-demand” release determines endocannabinoid signaling, their rapid degradation is expected to control the temporal profile of endocannabinoid action and may impact neuronal signaling. Here we show that memory formation through fear conditioning selectively accelerates the degradation of endocannabinoids in the cerebellum. Learning induced a lasting increase in GABA release and this was responsible for driving the change in endocannabinoid degradation. Conversely, Gq-DREADD activation of cerebellar Purkinje cells enhanced endocannabinoid signaling and impaired memory consolidation. Our findings identify a previously unappreciated reciprocal interaction between GABA and the endocannabinoid system in which GABA signaling accelerates endocannabinoid degradation, and triggers a form of learning-induced metaplasticity. Endocannabinoid levels are controlled by the fine balance between their synthesis and degradation. Here, the authors show that memory formation through fear conditioning selectively accelerates the degradation of endocannabinoids in the cerebellum via a lasting increase in GABA release.
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影响因子：
5.7
作者：
Castillo PE;Chiu CQ;Carroll RC
通讯作者：
Carroll RC
影响因子：
2.9
作者：
GUILLAUMIN, S;DAHHAOUI, M;CASTON, J
通讯作者：
CASTON, J
影响因子：
3.4
作者：
Chen Y;Liu X;Vickstrom CR;Liu MJ;Zhao L;Viader A;Cravatt BF;Liu QS
通讯作者：
Liu QS
DOI：
10.1073/pnas.1310983110
发表时间：
2013-12-03
影响因子：
11.1
作者：
Alcami, Pepe;Marty, Alain
通讯作者：
Marty, Alain
影响因子：
2.5
作者：
Dubois, C. J.;Ramamoorthy, P.;Liu, S. J.
通讯作者：
Liu, S. J.