2-AG and anandamide enhance hippocampal long-term potentiation via suppression of inhibition.
2-AG and anandamide enhance hippocampal long-term potentiation via suppression of inhibition.
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DOI：
10.3389/fncel.2022.1023541
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发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
人们普遍认为，外源性大麻素会损害人类和其他动物的短期记忆和认知。这可能与抑制长时程增强（LTP）有关，LTP是一种突触可塑性形式，在外源性激动剂存在下，CB 1大麻素受体的全局和持续激活。相反，内源性大麻素（eCB）配体的时间和空间限制性释放可以以突触特异性方式增强突触可塑性。通过记录幼年小鼠海马脑片CA 1区放射层的场兴奋性突触后电位（fEPSPs），研究eCB信号在LTP中的作用。通过θ爆发刺激（TBS）电诱导LTP，或通过用设计用于增加细胞内cAMP的溶液（chem-LTP）处理15分钟来电诱导LTP。通过CB 1受体拮抗剂阻断大麻素受体激活，TBS后fEPSP斜率的稳定和持久增强显著降低。Chem-LTP导致fEPSP斜率持续增加2倍，也被CB 1受体拮抗剂阻断。通过抑制内源性配体2-花生四烯酸甘油（2-AG）和花生四烯酸酰胺的合成，TBS-LTP部分降低。用chem-LTP观察到类似的效果。阻断抑制性突触可完全阻止CB 1受体拮抗剂或抑制eCB合成对TBS-LTP和chem-LTP的影响。这些结果表明，同时激活CB 1受体的2-AG和花生四烯酸增强TBS诱导的和药理学诱导的LTP，这种效果是通过抑制GABA能突触的抑制介导的。
It is widely accepted that exogenous cannabinoids can impair short-term memory and cognition in humans and other animals. This is likely related to the inhibition of long-term potentiation (LTP), a form of synaptic plasticity, by the global and sustained activation of CB1 cannabinoid receptors in the presence of exogenous agonists. Conversely, the temporally and spatially restricted release of endogenous cannabinoid (eCB) ligands may enhance synaptic plasticity in a synapse-specific manner. We examined the role of eCB signaling in LTP by recording field excitatory postsynaptic potentials (fEPSPs) in the CA1 stratum radiatum in hippocampal slices from juvenile mice. LTP was induced either electrically, by theta burst stimulation (TBS), or pharmacologically, by treatment for 15 min with a solution designed to increase intracellular cAMP (chem-LTP). A stable and long-lasting potentiation in fEPSP slope following TBS was significantly reduced by blocking cannabinoid receptor activation with CB1 receptor antagonists. Chem-LTP caused a sustained 2-fold increase in fEPSP slope and was also blocked by CB1 receptor antagonists. TBS-LTP was partially reduced by inhibiting the synthesis of the endogenous ligands 2-arachidonylglycerol (2-AG) and anandamide. A similar effect was observed with chem-LTP. Blocking inhibitory synapses completely prevented the effect of CB1 receptor antagonists or inhibition of eCB synthesis on TBS-LTP and chem-LTP. These results indicate that simultaneous activation of CB1 receptors by 2-AG and anandamide enhances TBS-induced and pharmacologically-induced LTP, and this effect is mediated by the suppression of inhibition at GABAergic synapses.
影响因子：
5.7
作者：
Younts TJ;Castillo PE
通讯作者：
Castillo PE