A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.
A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.
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DOI：
10.3389/fncel.2022.844243
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发表时间：
2022
影响因子：
5.3
通讯作者：
Scofield MD
中科院分区：
文献类型：
--
作者：
Siemsen BM;Barry SM;Vollmer KM;Green LM;Brock AG;Westphal AM;King RA;DeVries DM;Otis JM;Cowan CW;Scofield MD
额叶皮质投射到丘脑核的核心对于线索诱导的可卡因寻找是至关重要的，但是这种投射所靶向的丘脑神经元的身份以及这些细胞内导致复发的短暂神经适应仍然未知。雄性Sprague-Dawley大鼠接受可卡因或蔗糖自我给药、消退和线索诱导的恢复。通路特异性化学遗传学，膜片钳电生理学，在体内电化学，和高分辨率共聚焦显微镜被用来识别和表征一个小的人口的核心神经元，接受密集的前边缘皮层输入，以确定其在调节线索诱导的可卡因和自然的奖励寻求的作用。化学发生抑制的前边缘皮质投射到核cubens核心抑制线索诱导的可卡因复发和正常化的实时线索诱发的增加cubens谷氨酸释放的蔗糖寻求动物。此外，化学发生抑制的人口的nucleus核心神经元接收denefined prelimbic皮质输入抑制可卡因，但不蔗糖寻求。这些神经元也经历了形态可塑性的高峰期可卡因寻求树突棘扩张的形式和增加ensheathment在大的棘星形胶质细胞的过程。我们确定并表征了一个独特的亚群，接受密集的前边缘皮层输入的核神经元。这个亚群的功能特异性是强调他们的能力，介导线索诱导的可卡因复吸，但不是蔗糖寻求。这个细胞亚群代表了成瘾治疗的一个新靶点，它是通过顺行靶向询问嵌入在已知网络中的功能回路而发现的。
Prelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown. Male Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking. Chemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines. We identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.
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影响因子：
3.7
作者：
Klug JR;Mathur BN;Kash TL;Wang HD;Matthews RT;Robison AJ;Anderson ME;Deutch AY;Lovinger DM;Colbran RJ;Winder DG
通讯作者：
Winder DG
DOI：
10.1016/j.pnpbp.2018.01.002
发表时间：
2018-12-20
影响因子：
5.6
作者：
Farrell MR;Schoch H;Mahler SV
通讯作者：
Mahler SV
影响因子：
3.4
作者：
Siemsen BM;Lombroso PJ;McGinty JF
通讯作者：
McGinty JF
影响因子：
5.3
作者：
Augur, Isabel F.;Wyckoff, Andrew R.;Peters, Jamie
通讯作者：
Peters, Jamie
影响因子：
5.3
作者：
Keaveney, Marianna K.;Rahsepar, Bahar;Han, Xue
通讯作者：
Han, Xue