Molecular composition of the endocannabinoid system at glutamatergic synapses
Molecular composition of the endocannabinoid system at glutamatergic synapses
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DOI：
10.1523/jneurosci.0309-06.2006
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发表时间：
2006-05-24
影响因子：
5.3
通讯作者：
Freund, Tamás F.
中科院分区：
文献类型：
--
作者：
Katona, István;Urbán, Gabriella M.;Freund, Tamás F.
内源性大麻素在整个CNS的各种突触的逆行信号传导中发挥核心作用。虽然内源性大麻素系统的几个分子成分已被确定最近，其精确的位置和逆行突触信号的贡献是基本上是未知的。在这里，我们表明，通过使用两个独立的核糖探针，海马的主要细胞群体表达高水平的二酰基甘油脂肪酶α（DGL-α），参与生成内源性大麻素2-花生四烯酸-甘油（2-AG）的酶。两个独立的抗体对DGL-α的免疫染色显示，这种脂肪酶集中在整个海马结构的树突棘的头部。此外，定量的高分辨率免疫电镜数据表明，这种酶是高度区室化成一个广泛的突触周环周围的突触后密度的轴棘接触，但没有发生突触内。在突触的另一侧，形成这些兴奋性接触的轴突末梢被发现配备有突触前CB 1大麻素受体。这种精确的解剖定位表明，2-AG产生的DGL-α的脊椎头可能参与逆行突触信号在突触能突触，而CB 1受体位于传入末梢的理想位置结合2-AG，从而调节突触前谷氨酸释放作为突触后活动的函数。我们建议，这种内源性大麻素系统的分子组成可能是一个普遍的特点，大多数mammatergic突触在整个大脑，并可能有助于同源突触可塑性的兴奋性突触和异突触可塑性之间的兴奋性和抑制性接触。
Endocannabinoids play central roles in retrograde signaling at a wide variety of synapses throughout the CNS. Although several molecular components of the endocannabinoid system have been identified recently, their precise location and contribution to retrograde synaptic signaling is essentially unknown. Here we show, by using two independent riboprobes, that principal cell populations of the hippocampus express high levels of diacylglycerol lipase alpha (DGL-alpha), the enzyme involved in generation of the endocannabinoid 2-arachidonoyl-glycerol(2-AG). Immunostaining with two independent antibodies against DGL-alpha revealed that this lipase was concentrated in heads of dendritic spines throughout the hippocampal formation. Furthermore, quantification of high-resolution immunoelectron microscopic data showed that this enzyme was highly compartmentalized into a wide perisynaptic annulus around the postsynaptic density of axospinous contacts but did not occur intrasynaptically. On the opposite side of the synapse, the axon terminals forming these excitatory contacts were found to be equipped with presynaptic CB1 cannabinoid receptors. This precise anatomical positioning suggests that 2-AG produced by DGL-alpha on spine heads may be involved in retrograde synaptic signaling at glutamatergic synapses, whereas CB1 receptors located on the afferent terminals are in an ideal position to bind 2-AG and thereby adjust presynaptic glutamate release as a function of postsynaptic activity. We propose that this molecular composition of the endocannabinoid system may be a general feature of most glutamatergic synapses throughout the brain and may contribute to homosynaptic plasticity of excitatory synapses and to heterosynaptic plasticity between excitatory and inhibitory contacts.