Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Nat Neurosci. 2010 Dec;13(12):1519-25. doi: 10.1038/nn.2685. Epub 2010 Nov 14.
Synaptic modifications in the nucleus accumbens (NAc) are important for adaptive and pathological reward-dependent learning. Medium spiny neurons (MSNs), the major cell type in the NAc, participate in two parallel circuits that subserve distinct behavioral functions, yet little is known about differences in their electrophysiological and synaptic properties. Using bacterial artificial chromosome transgenic mice, we found that synaptic activation of group I metabotropic glutamate receptors in NAc MSNs in the indirect, but not direct, pathway led to the production of endocannabinoids, which activated presynaptic CB1 receptors to trigger endocannabinoid-mediated long-term depression (eCB-LTD) as well as postsynaptic transient receptor potential vanilloid 1 (TRPV1) channels to trigger a form of LTD resulting from endocytosis of AMPA receptors. These results reveal a previously unknown action of TRPV1 channels and indicate that the postsynaptic generation of endocannabinoids can modulate synaptic strength in a cell type-specific fashion by activating distinct pre- and postsynaptic targets.
伏隔核（NAc）中的突触修饰对于适应性和病理性的奖赏依赖学习很重要。中脑腹侧被盖区神经元（MSNs）是 NAc 中的主要细胞类型，参与两个平行的回路，分别发挥不同的行为功能，但它们在电生理和突触特性上的差异知之甚少。利用细菌人工染色体转基因小鼠，我们发现 NAc MSNs 中的 I 组代谢型谷氨酸受体的突触激活会导致内源性大麻素的产生，内源性大麻素激活突触前 CB1 受体，引发内源性大麻素介导的长时程抑制（eCB-LTD），同时激活瞬时受体电位香草酸 1（TRPV1）通道，引发 AMPA 受体内吞导致的 LTD 形式。这些结果揭示了 TRPV1 通道的一个先前未知的作用，并表明内源性大麻素的突触后产生可以通过激活不同的突触前和突触后靶标，以细胞类型特异性的方式调节突触强度。
