Cocaine memory reactivation induces functional adaptations within parvalbumin interneurons in the rat medial prefrontal cortex,Addiction Biology

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Cocaine memory reactivation induces functional adaptations within parvalbumin interneurons in the rat medial prefrontal cortex
Addiction Biology ( IF 3.1 ) Pub Date : 2020-08-04 , DOI: 10.1111/adb.12947
Emily T Jorgensen _{1,

2} , Angela E Gonzalez _{3,

4} , John H Harkness ₃ , Deborah M Hegarty ₅ , Amit Thakar _{1,

2} , Delta J Burchi ₂ , Jake A Aadland ₂ , Sue A Aicher ₅ , Barbara A Sorg _{3,

4} , Travis E Brown _{1,

2}

Affiliation

Substance use disorder is a complex disease created in part by maladaptive learning and memory mechanisms following repeated drug use. Exposure to drug‐associated stimuli engages prefrontal cortex circuits, and dysfunction of the medial prefrontal cortex (mPFC) is thought to underlie drug‐seeking behaviors. Growing evidence supports a role for parvalbumin containing fast‐spiking interneurons (FSI) in modulating prefrontal cortical microcircuit activity by influencing the balance of excitation and inhibition, which can influence learning and memory processes. Most parvalbumin FSIs within layer V of the prelimbic mPFC are surrounded by specialized extracellular matrix structures called perineuronal nets (PNN). Previous work by our group found that cocaine exposure altered PNN‐surrounded FSI function, and pharmacological removal of PNNs reduced cocaine‐seeking behavior. However, the role of FSIs and associated constituents (parvalbumin and PNNs) in cocaine‐related memories was not previously explored and is still unknown. Here, we found that reactivation of a cocaine conditioned place preference memory produced changes in cortical PNN‐surrounded parvalbumin FSIs, including decreased parvalbumin intensity, increased parvalbumin cell axis diameter, decreased intrinsic excitability, and increased excitatory synaptic input. Further investigation of intrinsic properties revealed changes in the interspike interval, membrane capacitance, and afterhyperpolarization recovery time. Changes in these specific properties suggest an increase in potassium‐mediated currents, which was validated with additional electrophysiological analysis. Collectively, our results indicate that cocaine memory reactivation induces functional adaptations in PNN‐surrounded parvalbumin neurons, which likely alters cortical output to promote cocaine‐seeking behavior.

中文翻译：

可卡因记忆重新激活诱导大鼠内侧前额叶皮层小清蛋白中间神经元的功能适应

药物滥用障碍是一种复杂的疾病，部分原因是重复使用药物后适应不良的学习和记忆机制。暴露于与药物相关的刺激会影响前额叶皮层回路，而内侧前额叶皮层（mPFC）的功能障碍被认为是药物寻求行为的基础。越来越多的证据支持含有快速尖峰中间神经元（FSI）的小白蛋白通过影响兴奋和抑制的平衡来调节前额皮质微电路活动，从而影响学习和记忆过程。前缘 mPFC 第五层内的大多数小白蛋白 FSI 被称为神经元周围网 (PNN) 的特殊细胞外基质结构包围。我们小组之前的研究发现，接触可卡因会改变 PNN 周围的 FSI 功能，并且通过药物去除 PNN 会减少寻求可卡因的行为。然而，FSIs 和相关成分（小清蛋白和 PNN）在可卡因相关记忆中的作用以前没有被探索过，而且仍然未知。在这里，我们发现可卡因条件性位置偏好记忆的重新激活会导致皮质 PNN 周围的小清蛋白 FSI 发生变化，包括小清蛋白强度降低、小清蛋白细胞轴直径增加、内在兴奋性降低和兴奋性突触输入增加。对内在特性的进一步研究揭示了尖峰间隔、膜电容和超极化后恢复时间的变化。这些特定特性的变化表明钾介导的电流增加，这一点通过额外的电生理学分析得到了验证。总的来说，我们的结果表明可卡因记忆重新激活会诱导 PNN 周围的小白蛋白神经元的功能适应，这可能会改变皮质输出以促进可卡因寻求行为。

更新日期：2020-08-04

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