University of Washington, Department of Biology, Seattle, WA 98195, USA.
J Neurophysiol. 2011 Mar;105(3):1159-69. doi: 10.1152/jn.00676.2010. Epub 2010 Dec 22.
Activation of type 1 cannabinoid receptors (CB(1)R) in many central nervous system structures induces both short- and long-term changes in synaptic transmission. Within mammalian striatum, endocannabinoids (eCB) are one of several mechanisms that induce synaptic plasticity at glutamatergic terminals onto medium spiny neurons. Striatal synaptic plasticity may contribute a critical component of adaptive motor coordination and procedural learning. Songbirds are advantageous for studying the neural mechanisms of motor learning because they possess a neural pathway necessary for song learning and adult song plasticity that includes a striato-pallidal nucleus, area X (homologous to a portion of mammalian basal ganglia). Recent findings suggest that eCBs contribute to vocal development. For example, dense CB(1)R expression in song control nuclei peaks around the closure of the sensori-motor integration phase of song development. Also, systemic administration of a CB(1)R agonist during vocal development impairs song learning. Here we test whether activation of CB(1)R alters excitatory synaptic input on spiny neurons in area X of adult male zebra finches. Application of the CB(1)R agonist WIN55212-2 decreased excitatory postsynaptic current (EPSC) amplitude; that decrease was blocked by the CB(1)R antagonist AM251. Guided by eCB experiments in mammalian striatum, we tested and verified that at least two mechanisms indirectly activate CB(1)Rs through eCBs in area X. First, activation of group I metabotropic glutamate receptors with the agonist 3,5-dihydroxyphenylglycine (DHPG) induced a CB(1)R-mediated reduction in EPSC amplitude. Second, we observed that a 10 s postsynaptic depolarization induced a calcium-mediated, eCB-dependent decrease in synaptic strength that resisted rescue with late CB(1)R blockade. Together, these results show that eCB modulation occurs at inputs to area X spiny neurons and could influence motor learning and production.
1 型大麻素受体（CB1R）在许多中枢神经系统结构中的激活会导致突触传递的短期和长期变化。在哺乳动物纹状体中，内源性大麻素（eCB）是诱导谷氨酸能末梢到中等棘神经元突触可塑性的几种机制之一。纹状体突触可塑性可能是适应性运动协调和程序性学习的关键组成部分。鸣禽在研究运动学习的神经机制方面具有优势，因为它们具有学习鸣唱和成年鸣唱可塑性所需的神经通路，包括纹状体-苍白球核、区域 X（与哺乳动物基底神经节的一部分同源）。最近的研究结果表明，eCB 有助于发声发育。例如，在鸣唱发育的感觉-运动整合阶段接近关闭时，控制核中的 CB1R 表达密集。此外，在发声发育过程中全身给予 CB1R 激动剂会损害鸣唱学习。在这里，我们测试了 CB1R 的激活是否会改变成年雄性斑马雀区域 X 中棘神经元的兴奋性突触输入。CB1R 激动剂 WIN55212-2 的应用降低了兴奋性突触后电流（EPSC）幅度；该降低被 CB1R 拮抗剂 AM251 阻断。受哺乳动物纹状体中 eCB 实验的指导，我们测试并验证了至少有两种机制通过区域 X 中的 eCB 间接激活 CB1R。首先，用激动剂 3,5-二羟基苯甘氨酸（DHPG）激活 I 型代谢型谷氨酸受体，诱导 CB1R 介导的 EPSC 幅度降低。其次，我们观察到 10 秒的突触后去极化诱导钙介导的、eCB 依赖性的突触强度降低，这种降低无法通过后期 CB1R 阻断来挽救。总之，这些结果表明 eCB 调节发生在区域 X 棘神经元的输入部位，可能影响运动学习和产生。
