Voltage drives diverse endocannabinoid signals to mediate striatal microcircuit-specific plasticity.

Voltage drives diverse endocannabinoid signals to mediate striatal microcircuit-specific plasticity.
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DOI:
10.1038/nn.3478
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发表时间:
2013-09
影响因子:
25
通讯作者:
Lovinger, David M.
Lovinger, David M.
中科院分区:
医学1区
文献类型:
--
作者:
Mathur, Brian N.;Tanahira, Chiyoko;Tamamaki, Nobuaki;Lovinger, David M.

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背外侧纹状体和大麻素1型受体(CB 1)信号传导介导习惯性动作学习,这被认为需要直接和间接纹状体输出通路中的活性平衡。然而,很少有人知道如何高CB 1表达纹状体抑制性微电路可能有助于长期可塑性能够雕刻直接/间接途径输出。利用纹状体GABA能微电路的光遗传学和分子询问,我们描述了小鼠和大鼠中棘投射神经元(MSN)的抑制性突触(iLTD)的电压依赖性长期抑制的新机制。这种iLTD涉及募集不同的内源性大麻素类型,并显示出对MSN亚型的突触前和突触后选择性,最终导致直接途径MSN的强大去抑制。这些结果表明,在门控电路特定形式的突触可塑性的电压状态的一个新的角色,并照亮可能的电路动态动作控制。
The dorsolateral striatum and cannabinoid type 1 receptor (CB1) signaling mediate habitual action learning, which is thought to require a balance of activity in the direct and indirect striatal output pathways. However, very little is known about how the high CB1-expressing striatal inhibitory microcircuitry might contribute to long-term plasticity capable of sculpting direct/indirect pathway output. Using optogenetic and molecular interrogation of striatal GABAergic microcircuits, we describe novel mechanisms of voltage-dependent long-term depression of inhibitory synapses (iLTD) onto mouse and rat medium spiny projection neurons (MSNs). This iLTD involves recruitment of different endocannabinoid types and shows both presynaptic and postsynaptic selectivity for MSN subtypes, ultimately resulting in a powerful disinhibition of direct pathway MSNs. These results indicate a new role for voltage states in gating circuit-specific forms of synaptic plasticity and illuminate possible circuit dynamics underlying action control.
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