Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons in the forebrain controls glutamatergic synaptic transmission
Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons in the forebrain controls glutamatergic synaptic transmission
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DOI：
10.1523/jneurosci.0372-06.2006
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发表时间：
2006-05-24
影响因子：
5.3
通讯作者：
Rammes, Gerhard
中科院分区：
文献类型：
--
作者：
Domenici, Maria R.;Azad, Shahnaz C.;Rammes, Gerhard
大麻素通过激活大麻素受体1（CB 1）来调节GABA的释放。从各种大脑区域获得的结果一致表明，大麻素激动剂也可以减少多巴胺能突触传递。然而，关于CB 1在大麻素诱导的抑制皮质区的多巴胺能传递中的作用，仍然存在相互矛盾的数据。在这里，我们提供了直接的证据表明，激活CB 1对终端的主要神经元控制兴奋性突触反应在前脑。在野生型小鼠的基底外侧杏仁核、海马CA 1区和初级躯体感觉皮层切片中，应用CB 1激动剂（R）-（+）-[2，3-二氢-5-甲基-3-（4-吗啉基甲基）吡咯并[1，2，3-de]-1，4-苯并恶嗪-6-基]-1-萘甲酮（WIN 55，212-2; WIN）（5 μ M）可减少诱发的兴奋性突触后反应。相比之下，在所有主要前脑神经元中缺乏CB 1但在GABA能中间神经元中没有CB 1（f/f;CaMKII alpha Cre）的条件性小鼠突变体中获得的切片中，WIN不再影响任何测试的大脑区域中的突触传递。与突触前机制相兼容，WIN没有改变对局部未封闭的L-谷氨酸的敏感性。WIN减少了从仅在GABA能神经元中缺乏CB 1的小鼠获得的切片中的多巴胺能反应（CB 1（f/f; Dlx 5/6-Cre）），因此排除了在药物的这种作用中在GABA能神经元上表达的CB 1的参与。目前的数据有力地表明，兴奋性突触传递在前脑区直接调制的CB 1表达的突触前轴突末梢起源于海马能神经元。
It is widely accepted that cannabinoids regulate GABA release by activation of cannabinoid receptor type 1 (CB1). Results obtained from a variety of brain regions consistently indicate that cannabinoid agonists can also reduce glutamatergic synaptic transmission. However, there are still conflicting data concerning the role of CB1 in cannabinoid-induced inhibition of glutamatergic transmission in cortical areas. Here, we provide direct evidence that activation of CB1 on terminals of principal neurons controls excitatory synaptic responses in the forebrain. In slices of the basolateral amygdala, the CA1 region of the hippocampus, and the primary somatosensory cortex of wild-type mice, application of the CB1 agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55,212-2; WIN) (5 mu M) reduced evoked excitatory postsynaptic responses. In contrast, in slices obtained from conditional mouse mutants lacking CB1 in all principal forebrain neurons but not in GABAergic interneurons (CB1(f/f;CaMKII alpha Cre)), WIN no longer affected glutamatergic synaptic transmission in any of the brain regions tested. Compatible with a presynaptic mechanism, WIN did not change the sensitivity to focally uncaged L-glutamate. WIN reduced glutamatergic responses in slices obtained from mice lacking CB1 exclusively in GABAergic neurons (CB1(f/f;Dlx5/6-Cre)), thus excluding the involvement of CB1 expressed on GABAergic neurons in this effect of the drug. The present data strongly indicate that excitatory synaptic transmission in forebrain areas is directly modulated by CB1 expressed on presynaptic axon terminals originating from glutamatergic neurons.