Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses

Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses
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DOI:
10.1152/jn.00980.2010
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发表时间:
2011-02-01
影响因子:
2.5
通讯作者:
Regehr, Wade G.
Regehr, Wade G.
中科院分区:
医学3区
文献类型:
--
作者:
Carey, Megan R.;Myoga, Michael H.;Regehr, Wade G.

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Carey MR,Myoga MH,McDaniels KR,Marsicano G,Lutz B,Mackie K,Regehr WG.突触前CB 1受体调节小脑平行纤维突触的突触可塑性。J Neurophysiol 105:958-963,2011.首次发表于2010年11月17日; doi:10.1152/jn.00980.2010。内源性大麻素是突触强度的有效调节剂。它们通常被认为通过突触前1型大麻素受体(CB 1 R)的逆行激活来改变神经递质的释放。在小脑皮质,CB 1 Rs调节几种形式的突触可塑性在突触上浦肯野细胞,包括突触前表达的短期可塑性,有点矛盾,突触后形式的长期抑郁症(LTD)。在这里,我们已经产生了小鼠,其中CB 1 Rs被选择性地从小脑颗粒细胞中消除,其轴突形成平行纤维。我们发现,在这些小鼠中,内源性大麻素依赖的短期可塑性被消除在平行纤维,但不是抑制性中间神经元,突触到浦肯野细胞。此外,在这些小鼠中没有观察到平行纤维LTD,表明突触前CB 1 R调节该突触的长期可塑性。
Carey MR, Myoga MH, McDaniels KR, Marsicano G, Lutz B, Mackie K, Regehr WG. Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses. J Neurophysiol 105: 958-963, 2011. First published November 17, 2010; doi: 10.1152/jn.00980.2010. Endocannabinoids are potent regulators of synaptic strength. They are generally thought to modify neurotransmitter release through retrograde activation of presynaptic type 1 cannabinoid receptors (CB1Rs). In the cerebellar cortex, CB1Rs regulate several forms of synaptic plasticity at synapses onto Purkinje cells, including presynaptically expressed short-term plasticity and, somewhat paradoxically, a postsynaptic form of long-term depression (LTD). Here we have generated mice in which CB1Rs were selectively eliminated from cerebellar granule cells, whose axons form parallel fibers. We find that in these mice, endocannabinoid-dependent short-term plasticity is eliminated at parallel fiber, but not inhibitory interneuron, synapses onto Purkinje cells. Further, parallel fiber LTD is not observed in these mice, indicating that presynaptic CB1Rs regulate long-term plasticity at this synapse.