Endocannabinoids mediate synaptic plasticity at glutamatergic synapses on spiny neurons within a basal ganglia nucleus necessary for song learning.
Endocannabinoids mediate synaptic plasticity at glutamatergic synapses on spiny neurons within a basal ganglia nucleus necessary for song learning.
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内源性大麻素介导基底神经节核内多刺神经元谷氨酸突触的突触可塑性，这是歌曲学习所必需的。
DOI：
10.1152/jn.00676.2010
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发表时间：
2011
影响因子：
2.5
通讯作者：
Perkel,DavidJ
中科院分区：
文献类型：
--
作者：
Thompson,JohnA;Perkel,DavidJ
在许多中枢神经系统结构中，1型大麻素受体（CB 1 R）的激活诱导突触传递的短期和长期变化。在哺乳动物纹状体内，内源性大麻素（eCB）是在中棘神经元上的多巴胺能末梢诱导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重要组成部分。鸣禽对于研究运动学习的神经机制是有利的，因为它们具有歌曲学习和成年歌曲可塑性所必需的神经通路，包括纹状体苍白球核，X区（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有助于发声发展。例如，密集的CB 1 R表达在歌曲控制核的峰值关闭的感觉运动整合期的歌曲发展。此外，在发声发育过程中全身给予CB 1 R激动剂会损害歌曲学习。在这里，我们测试是否激活CB 1 R改变兴奋性突触输入的刺神经元在X区的成年雄性斑胸草雀。CB 1 R激动剂WIN 55212 -2的应用降低了兴奋性突触后电流（EPSC）的幅度;这种降低被CB 1 R拮抗剂AM 251阻断。在哺乳动物纹状体eCB实验的指导下，我们测试并验证了至少两种机制通过eCB间接激活X区的CB 1 R。首先，用激动剂3，5-二羟基苯甘氨酸（DHPG）激活I组代谢型谷氨酸受体诱导CB 1 R介导的EPSC振幅降低。其次，我们观察到，10秒突触后去极化诱导钙介导的，eCB依赖性突触强度的降低，抵抗救援与晚期CB 1 R阻滞。总之，这些结果表明，eCB调制发生在输入到X区棘神经元，并可能影响运动学习和生产。
Activation of type 1 cannabinoid receptors (CB1R) 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 CB1R expression in song control nuclei peaks around the closure of the sensori-motor integration phase of song development. Also, systemic administration of a CB1R agonist during vocal development impairs song learning. Here we test whether activation of CB1R alters excitatory synaptic input on spiny neurons in area X of adult male zebra finches. Application of the CB1R agonist WIN55212–2 decreased excitatory postsynaptic current (EPSC) amplitude; that decrease was blocked by the CB1R antagonist AM251. Guided by eCB experiments in mammalian striatum, we tested and verified that at least two mechanisms indirectly activate CB1Rs through eCBs in area X. First, activation of group I metabotropic glutamate receptors with the agonist 3,5-dihydroxyphenylglycine (DHPG) induced a CB1R-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 CB1R blockade. Together, these results show that eCB modulation occurs at inputs to area X spiny neurons and could influence motor learning and production.