Cocaine Experience Enhances Thalamo-Accumbens N-Methyl-D-Aspartate Receptor Function.
Cocaine Experience Enhances Thalamo-Accumbens N-Methyl-D-Aspartate Receptor Function.
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可卡因经验增强了丘脑 - 辅助n-甲基-D-天冬氨酸受体功能。
DOI：
10.1016/j.biopsych.2016.04.002
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发表时间：
2016-11-01
影响因子：
10.6
通讯作者：
Grueter, Brad A.
中科院分区：
文献类型：
--
作者：
Joffe, Max E.;Grueter, Brad A.
兴奋性突触传递在丘脑核（NAc）是一个关键的生物基质的行为反应的精神兴奋剂和易感性复发。最近的研究表明，可卡因在不同的输入NAc诱导的多巴胺能信号的变化。然而，可卡因的经验，从丘脑中线核（mThal）到NAc的突触传递的后果尚未报道。为了检查来自特定NAc核心输入的突触，我们记录了急性脑切片中mThal、前额叶皮质（PFC）或基底外侧杏仁核（BLA）中的视紫红质通道蛋白-2病毒介导表达后的光诱发兴奋性突触后电流（EPSC）。为了鉴定NAc中等多刺神经元（MSN）亚型，我们利用表达由多巴胺受体亚型1（D1）的启动子驱动的tdTomato的小鼠。我们记录了N-甲基-D-天冬氨酸受体（NMDAR）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的特性，以评估可卡因经验（5天可卡因暴露，随后2周戒断）诱导的突触适应。我们确定，NAc核心的兴奋性输入显示出不同的NMDAR特性，可卡因体验独特地改变了mThal-D1（+）、mThal-D1（-）和PFC-D1（+）突触的AMPAR和NMDAR特性，但不改变PFC-D1（-）突触。最后，在mThal-D1（+）突触，我们证明可卡因增强GluN 2C/D功能和NMDAR依赖的突触可塑性。我们的研究结果确定了对比可卡因诱导的AMPAR和NMDAR修改mThal和PFC-NAc核心突触。这些变化包括NMDAR功能的增强和mThal-D1（+）突触的可塑性。包含GluN 2C/D的NMDAR的掺入最有可能是这些现象的基础，并且代表了精神兴奋剂使用障碍的潜在治疗靶点。
Excitatory synaptic transmission in the nucleus accumbens (NAc) is a key biological substrate underlying behavioral responses to psychostimulants and susceptibility to relapse. Recent studies have demonstrated that cocaine induces changes in glutamatergic signaling at distinct inputs to the NAc. However, consequences of cocaine experience on synaptic transmission from the midline nuclei of the thalamus (mThal) to the NAc have yet to be reported. To examine synapses from specific NAc core inputs, we recorded light-evoked excitatory postsynaptic currents (EPSCs) following viral-mediated expression of channelrhodopsin-2 in the mThal, prefrontal cortex (PFC), or basolateral amygdala (BLA) from acute brain slices. To identify NAc medium spiny neuron (MSN) subtypes we utilized mice expressing tdTomato driven by the promoter for the dopamine receptor subtype 1 (D1). We recorded N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) properties to evaluate synaptic adaptations induced by cocaine experience, a 5-day cocaine exposure followed by 2-weeks of abstinence. We determine that excitatory inputs to the NAc core display differential NMDAR properties and cocaine experience uniquely alters AMPAR and NMDAR properties at mThal-D1(+), mThal-D1(−), and PFC-D1(+) synapses, but not PFC-D1(−) synapses. Finally, at mThal-D1(+) synapses, we demonstrate that cocaine enhances GluN2C/D function and NMDAR-dependent synaptic plasticity. Our results identify contrasting cocaine-induced AMPAR and NMDAR modifications at mThal- and PFC-NAc core synapses. These changes include an enhancement of NMDAR function and plasticity at mThal-D1(+) synapses. Incorporation of GluN2C/D-containing NMDARs most likely underlies these phenomena and represents a potential therapeutic target for psychostimulant use disorders.
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影响因子：
4.2
作者：
Browning, Jenny R.;Jansen, Heiko T.;Sorg, Barbara A.
通讯作者：
Sorg, Barbara A.
影响因子：
3.9
作者：
Joffe, Max E.;Grueter, Carrie A.;Grueter, Brad A.
通讯作者：
Grueter, Brad A.
影响因子：
25
作者：
Bock, Roland;Shin, J. Hoon;Kaplan, Alanna R.;Dobi, Alice;Markey, Eric;Kramer, Paul F.;Gremel, Christina M.;Christensen, Christine H.;Adrover, Martin F.;Alvarez, Veronica A.
通讯作者：
Alvarez, Veronica A.
影响因子：
7.6
作者：
Jedynak, Jakub;Hearing, Matthew;Thomas, Mark J.
通讯作者：
Thomas, Mark J.
DOI：
10.1073/pnas.1221742110
发表时间：
2013-01-29
影响因子：
11.1
作者：
Grueter, Brad A.;Robison, Alfred J.;Malenka, Robert C.
通讯作者：
Malenka, Robert C.