当前位置: X-MOL 学术Front. Cell. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Drugs of Abuse Differentially Alter the Neuronal Excitability of Prefrontal Layer V Pyramidal Cell Subtypes.
Frontiers in Cellular Neuroscience ( IF 5.3 ) Pub Date : 2021-08-05 , DOI: 10.3389/fncel.2021.703655
Jonna M Leyrer-Jackson 1 , Lauren E Hood 1 , M Foster Olive 1
Affiliation  

The medial prefrontal cortex (mPFC) plays an important role in regulating executive functions including reward seeking, task flexibility, and compulsivity. Studies in humans have demonstrated that drugs of abuse, including heroin, cocaine, methamphetamine, and alcohol, alter prefrontal function resulting in the consequential loss of inhibitory control and increased compulsive behaviors, including drug seeking. Within the mPFC, layer V pyramidal cells, which are delineated into two major subtypes (type I and type II, which project to subcortical or commissurally to other cortical regions, respectively), serve as the major output cells which integrate information from other cortical and subcortical regions and mediate executive control. Preclinical studies examining changes in cellular physiology in the mPFC in response to drugs of abuse, especially in regard to layer V pyramidal subtypes, are relatively sparse. In the present study, we aimed to explore how heroin, cocaine, methamphetamine, ethanol, and 3,4-methylenedioxypyrovalerone (MDPV) alter the baseline cellular physiology and excitability properties of layer V pyramidal cell subtypes. Specifically, animals were exposed to experimenter delivered [intraperitoneal (i.p.)] heroin, cocaine, the cocaine-like synthetic cathinone MDPV, methamphetamine, ethanol, or saline as a control once daily for five consecutive days. On the fifth day, whole-cell physiology recordings were conducted from type I and type II layer V pyramidal cells in the mPFC. Changes in cellular excitability, including rheobase (i.e., the amount of injected current required to elicit action potentials), changes in input/output curves, as well as spiking characteristics induced by each substance, were assessed. We found that heroin, cocaine, methamphetamine, and MDPV decreased the excitability of type II cells, whereas ethanol increased the excitability of type I pyramidal cells. Together, these results suggest that heroin, cocaine, MDPV, and methamphetamine reduce mPFC commissural output by reducing type II excitability, while ethanol increases the excitability of type I cells targeting subcortical structures. Thus, separate classes of abused drugs differentially affect layer V pyramidal subtypes in the mPFC, which may ultimately give rise to compulsivity and inappropriate synaptic plasticity underlying substance use disorders.

中文翻译:

滥用药物差异性地改变前额叶 V 层锥体细胞亚型的神经元兴奋性。

内侧前额叶皮层 (mPFC) 在调节执行功能方面发挥着重要作用,包括寻求奖励、任务灵活性和强迫性。对人类的研究表明,滥用药物,包括海洛因、可卡因、甲基苯丙胺和酒精,会改变前额叶功能,从而导致抑制性控制的丧失和强迫行为的增加,包括寻求毒品。在 mPFC 内,V 层锥体细胞被划分为两个主要亚型(I 型和 II 型,分别投射到皮层下或其他皮层区域),作为主要输出细胞,整合来自其他皮层和皮层的信息。皮层下区域和调节执行控制。临床前研究检查 mPFC 细胞生理学对滥用药物的反应,特别是在 V 层金字塔亚型方面,相对稀疏。在本研究中,我们旨在探索海洛因、可卡因、甲基苯丙胺、乙醇和 3,4-亚甲基二氧基吡咯戊酮 (MDPV) 如何改变 V 层锥体细胞亚型的基线细胞生理学和兴奋性特性。具体而言,将动物暴露于实验者递送的 [腹腔 (ip)] 海洛因、可卡因、可卡因样合成卡西酮 MDPV、甲基苯丙胺、乙醇或盐水作为对照,每天一次,连续五天。在第五天,从 mPFC 中的 I 型和 II 型 V 层锥体细胞进行全细胞生理学记录。细胞兴奋性的变化,包括 rheobase(即引发动作电位所需的注入电流量),输入/输出曲线的变化,以及由每种物质引起的尖峰特性,进行了评估。我们发现海洛因、可卡因、甲基苯丙胺和 MDPV 降低了 II 型细胞的兴奋性,而乙醇增加了 I 型锥体细胞的兴奋性。总之,这些结果表明海洛因、可卡因、MDPV 和甲基苯丙胺通过降低 II 型兴奋性来减少 mPFC 连合输出,而乙醇增加了靶向皮层下结构的 I 型细胞的兴奋性。因此,不同类别的滥用药物对 mPFC 中的 V 层锥体亚型有不同的影响,这可能最终导致物质使用障碍的强迫性和不适当的突触可塑性。而乙醇增加了 I 型锥体细胞的兴奋性。总之,这些结果表明海洛因、可卡因、MDPV 和甲基苯丙胺通过降低 II 型兴奋性来减少 mPFC 连合输出,而乙醇增加了靶向皮层下结构的 I 型细胞的兴奋性。因此,不同类别的滥用药物对 mPFC 中的 V 层锥体亚型有不同的影响,这可能最终导致物质使用障碍的强迫性和不适当的突触可塑性。而乙醇增加了 I 型锥体细胞的兴奋性。总之,这些结果表明海洛因、可卡因、MDPV 和甲基苯丙胺通过降低 II 型兴奋性来减少 mPFC 连合输出,而乙醇增加了靶向皮层下结构的 I 型细胞的兴奋性。因此,不同类别的滥用药物对 mPFC 中的 V 层锥体亚型有不同的影响,这可能最终导致物质使用障碍的强迫性和不适当的突触可塑性。
更新日期:2021-08-05
down
wechat
bug